Switzerland: cancer statistics from IARC GlobalCan (2012)
|Population in 2012: ||7.7m|
|People newly diagnosed with cancer (excluding NMSC) / yr: ||42,000|
|Age-standardised rate, incidence per 100,000 people/yr: ||287.0|
|Risk of getting cancer before age 75:||28.8%|
|People dying from cancer /yr: ||16,400|
Menu: Swiss Cancer Resources Swiss Cancer Organisations Recent Research Publications from Switzerland
Krebsliga Schweiz | Swiss Cancer League - Deutsch - Translate to English
A national, non-profit organisation, founded in 1910.
Scientific Association of Swiss Radiation Oncology
SASRO brings together radiation oncologists, radiation physicists, radiation biologists and radiographers in Switzerland to promote excellence in the field of radiotherapy. Radiation Oncology
Arbeitsgemeinschaft für Gynäkologische Onkologie und Brustgesundheit | Swiss Association of Gynecological Oncology - Deutsch - Translate to English
swiss-AGO Gynecologic Oncology
National Institute for Cancer Epidemiology and Registration
NICER aggregates data collected by the cantonal and regional cancer registries of Switzerland. The site includes statistics and publications. Cancer Registries
Schweizerische Pädiatrische Onkologie Gruppe | Swiss Paediatric Oncology Group - Deutsch - English
SPOG is a non-profit professional organisation, involved in research to achieve better treatment options and a higher quality of life for children and adolescents suffering from cancer. Pediatric Oncology Childhood Cancer
Schweizerische Patientenorganisation für Lymphombetroffene und angehörig | Swiss Patient Organization for Lymphoma Patients - Deutsch - Translate to English
Verein für Onkologische Pharmazie | Association for Oncology Pharmacy - Deutsch - Translate to English
A a non-profit association founded 2009. Oncology Pharmacy
A two-session psychological intervention for siblings of pediatric cancer patients: a randomized controlled pilot trial
Referenced research article; open access. Alice Prchal et al. Child and Adolescent Psychiatry and Mental Health 2012, 6:3 Siblings of Children with Cancer
An international, peer-reviewed open access journal on oncology from MDPI
Frontiers in Oncology
A journal which publishes articles on the most outstanding discoveries across a wide research spectrum of Oncology. Includes specialty sections.
ISREC: Swiss Institute for Experimental Cancer Research
Based at EPFL, Lausanne
Schweizerischen Arbeitsgemeinschaft für Klinische Krebsforschung | Swiss Group for Clinical Cancer Research - Deutsch - English
SAKK is a non-profit organization and cooperative association that has been conducting multicenter clinical trials independently of the pharmaceutical industry since 1965.
Swiss Childhood Cancer Registry
A national, population-based cancer registry located at the Institute of Social and Preventive Medicine (ISPM) at the University of Bern and closely co-operates with the Swiss Paediatric Oncology Group. Cancer Registries Childhood Cancer
Switzerland - European Cancer Observatory
Incidence, mortality and prevalence data and graphs.
Zhu AX, Kudo M, Assenat E, et al.Effect of everolimus on survival in advanced hepatocellular carcinoma after failure of sorafenib: the EVOLVE-1 randomized clinical trial.
JAMA. 2014; 312(1):57-67 [PubMed
] Related Publications
Aside from the multikinase inhibitor sorafenib, there are no effective systemic therapies for the treatment of advanced hepatocellular carcinoma.OBJECTIVE:
To assess the efficacy of everolimus in patients with advanced hepatocellular carcinoma for whom sorafenib treatment failed.DESIGN, SETTING, AND PARTICIPANTS:
EVOLVE-1 was a randomized, double-blind, phase 3 study conducted among 546 adults with Barcelona Clinic Liver Cancer stage B or C hepatocellular carcinoma and Child-Pugh A liver function whose disease progressed during or after sorafenib or who were intolerant of sorafenib. Patients were enrolled from 17 countries between May 2010 and March 2012. Randomization was stratified by region (Asia vs rest of world) and macrovascular invasion (present vs absent).INTERVENTIONS:
Everolimus, 7.5 mg/d, or matching placebo, both given in combination with best supportive care and continued until disease progression or intolerable toxicity. Per the 2:1 randomization scheme, 362 patients were randomized to the everolimus group and 184 patients to the placebo group.MAIN OUTCOMES AND MEASURES:
The primary end point was overall survival. Secondary end points included time to progression and the disease control rate (the percentage of patients with a best overall response of complete or partial response or stable disease).RESULTS:
No significant difference in overall survival was seen between treatment groups, with 303 deaths (83.7%) in the everolimus group and 151 deaths (82.1%) in the placebo group (hazard ratio [HR], 1.05; 95% CI, 0.86-1.27; P = .68; median overall survival, 7.6 months with everolimus, 7.3 months with placebo). Median time to progression with everolimus and placebo was 3.0 months and 2.6 months, respectively (HR, 0.93; 95% CI, 0.75-1.15), and disease control rate was 56.1% and 45.1%, respectively (P = .01). The most common grade 3/4 adverse events for everolimus vs placebo were anemia (7.8% vs 3.3%, respectively), asthenia (7.8% vs 5.5%, respectively), and decreased appetite (6.1% vs 0.5%, respectively). No patients experienced hepatitis C viral flare. Based on central laboratory results, hepatitis B viral reactivation was experienced by 39 patients (29 everolimus, 10 placebo); all cases were asymptomatic, but 3 everolimus recipients discontinued therapy.CONCLUSIONS AND RELEVANCE:
Everolimus did not improve overall survival in patients with advanced hepatocellular carcinoma whose disease progressed during or after receiving sorafenib or who were intolerant of sorafenib.TRIAL REGISTRATION:
clinicaltrials.gov Identifier: NCT01035229.Related: Liver Cancer Sorafenib (Nexavar) Everolimus (Afinitor)
Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston.
Gerber NU, von Hoff K, Resch A, et al.Treatment of children with central nervous system primitive neuroectodermal tumors/pinealoblastomas in the prospective multicentric trial HIT 2000 using hyperfractionated radiation therapy followed by maintenance chemotherapy.
Int J Radiat Oncol Biol Phys. 2014; 89(4):863-71 [PubMed
] Related Publications
The prognosis for children with central nervous system primitive neuroectodermal tumor (CNS-PNET) or pinealoblastoma is still unsatisfactory. Here we report the results of patients between 4 and 21 years of age with nonmetastatic CNS-PNET or pinealoblastoma diagnosed from January 2001 to December 2005 and treated in the prospective GPOH-trial P-HIT 2000-AB4.METHODS AND MATERIALS:
After surgery, children received hyperfractionated radiation therapy (36 Gy to the craniospinal axis, 68 Gy to the tumor region, and 72 Gy to any residual tumor, fractionated at 2 × 1 Gy per day 5 days per week) accompanied by weekly intravenous administration of vincristine and followed by 8 cycles of maintenance chemotherapy (lomustine, cisplatin, and vincristine).RESULTS:
Twenty-six patients (15 with CNS-PNET; 11 with pinealoblastoma) were included. Median age at diagnosis was 11.5 years old (range, 4.0-20.7 years). Gross total tumor resection was achieved in 6 and partial resection in 16 patients (indistinct, 4 patients). Median follow-up of the 15 surviving patients was 7.0 years (range, 5.2-10.0 years). The combined response rate to postoperative therapy was 17 of 20 (85%). Eleven of 26 patients (42%; 7 of 15 with CNS-PNET; 4 of 11 with pinealoblastoma) showed tumor progression or relapse at a median time of 1.3 years (range, 0.5-1.9 years). Five-year progression-free and overall survival rates (± standard error [SE]) were each 58% (± 10%) for the entire cohort: CNS-PNET was 53% (± 13); pinealoblastoma was 64% (± 15%; P=.524 and P=.627, respectively).CONCLUSIONS:
Postoperative hyperfractionated radiation therapy with local dose escalation followed by maintenance chemotherapy was feasible without major acute toxicity. Survival rates are comparable to those of a few other recent studies but superior to those of most other series, including the previous trial, HIT 1991.Related: Childhood Brain Tumours Childhood Brain Tumors
Department of Pediatric Oncology, University Children's Hospital, Zurich, Switzerland. Electronic address:
de Azambuja E, Procter MJ, van Veldhuisen DJ, et al.Trastuzumab-associated cardiac events at 8 years of median follow-up in the Herceptin Adjuvant trial (BIG 1-01).
J Clin Oncol. 2014; 32(20):2159-65 [PubMed
] Related Publications
To document the rate and outcome of trastuzumab-associated cardiac dysfunction in patients following 1 or 2 years of adjuvant therapy.PATIENTS AND METHODS:
The Herceptin Adjuvant (HERA) trial is a three-arm, randomized trial comparing 2 years or 1 year of trastuzumab with observation in 5,102 patients with human epidermal growth factor receptor 2 (HER2) -positive early-stage breast cancer. Cardiac function was closely monitored. Eligible patients had left ventricular ejection fraction (LVEF) ≥ 55% at study entry following neoadjuvant chemotherapy with or without radiotherapy. This 8-year median follow-up analysis considered patients randomly assigned to 2 years or 1 year of trastuzumab or observation.RESULTS:
The as-treated safety population for 2 years of trastuzumab (n = 1,673), 1 year of trastuzumab (n = 1,682), and observation (n = 1,744) is reported. Cardiac adverse events leading to discontinuation of trastuzumab occurred in 9.4% of patients in the 2-year arm and 5.2% of patients in the 1-year arm. Cardiac death, severe congestive heart failure (CHF), and confirmed significant LVEF decrease remained low in all three arms. The incidence of severe CHF (0.8%, 0.8%, and 0.0%, respectively) and confirmed significant LVEF decrease (7.2%, 4.1%, and 0.9%, respectively) was significantly higher in the 2-year and 1-year trastuzumab arms compared with the observation arm. Severe CHF was the same for 2-year and 1-year trastuzumab. Of patients with confirmed LVEF decrease receiving 2-year trastuzumab, 87.5% reached acute recovery. Of patients with confirmed LVEF decrease receiving 1-year trastuzumab, 81.2% reached acute recovery.CONCLUSION:
Long-term assessment at 8-year median follow-up confirms the low incidence of cardiac events for trastuzumab given sequentially after chemotherapy and radiotherapy, and cardiac events were reversible in the vast majority of patients.Related: Breast Cancer Trastuzumab (Herceptin)
Evandro de Azambuja and Martine J. Piccart-Genhart, Institut Jules Bordet; Evandro de Azambuja, Breast European Adjuvant Study Team; Martine J. Piccart-Gebhart, Université Libre de Bruxelles, Brussels, Belgium; Marion J. Procter and Dominique Agbor-Tarh, Frontier Science Scotland, Kincraig, Ki...
Gotta V, Bouchet S, Widmer N, et al.Large-scale imatinib dose-concentration-effect study in CML patients under routine care conditions.
Leuk Res. 2014; 38(7):764-72 [PubMed
] Related Publications
Division of Clinical Pharmacology, Service of Biomedicine, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland; School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Geneva, Switzerland.
Hottinger AF, Aissa AB, Espeli V, et al.Phase I study of sorafenib combined with radiation therapy and temozolomide as first-line treatment of high-grade glioma.
Br J Cancer. 2014; 110(11):2655-61 [PubMed
] Article available free on PMC
after 27/05/2015 Related Publications
Sorafenib (Sb) is a multiple kinase inhibitor targeting both tumour cell proliferation and angiogenesis that may further act as a potent radiosensitizer by arresting cells in the most radiosensitive cell cycle phase. This phase I open-label, noncontrolled dose escalation study was performed to determine the safety and maximum tolerated dose (MTD) of Sb in combination with radiation therapy (RT) and temozolomide (TMZ) in 17 patients with newly diagnosed high-grade glioma.METHODS:
Patients were treated with RT (60 Gy in 2 Gy fractions) combined with TMZ 75 mg m(-2) daily, and Sb administered at three dose levels (200 mg daily, 200 mg BID, and 400 mg BID) starting on day 8 of RT. Thirty days after the end of RT, patients received monthly TMZ (150-200 mg m(-2) D1-5/28) and Sb (400 mg BID). Pharmacokinetic (PK) analyses were performed on day 8 (TMZ) and on day 21 (TMZ&Sb) (Clinicaltrials ID: NCT00884416).RESULTS:
The MTD of Sb was established at 200 mg BID. Dose-limiting toxicities included thrombocytopenia (two patients), diarrhoea (one patient) and hypercholesterolaemia (one patient). Sb administration did not affect the mean area under the curve(0-24) and mean Cmax of TMZ and its metabolite 5-amino-imidazole-4-carboxamide (AIC). Tmax of both TMZ and AIC was delayed from 0.75 (TMZ alone) to 1.5 h (combined TMZ/Sb). The median progression-free survival was 7.9 months (95% confidence interval (CI): 5.4-14.55), and the median overall survival was 17.8 months (95% CI: 14.7-25.6).CONCLUSIONS:
Although Sb can be combined with RT and TMZ, significant side effects and moderate outcome results do not support further clinical development in malignant gliomas. The robust PK data of the TMZ/Sb combination could be useful in other cancer settings.Related: Dacarbazine Sorafenib (Nexavar) Temozolomide
1] Clinical Research Unit of the Foundation Dr Henri Dubois Ferriére Dinu Lipatti & Centre of Oncology, Geneva University Hospitals and University of Geneva, Geneva, Switzerland  Department of Clinical Neurosciences & Oncology, CHUV University Hospital and University of Lausanne, Lausanne, ...
Miller KD, Diéras V, Harbeck N, et al.Phase IIa trial of trastuzumab emtansine with pertuzumab for patients with human epidermal growth factor receptor 2-positive, locally advanced, or metastatic breast cancer.
J Clin Oncol. 2014; 32(14):1437-44 [PubMed
] Related Publications
Our phase IIa study characterized the safety and efficacy of two human epidermal growth factor receptor 2 (HER2) -targeted agents, trastuzumab emtansine (T-DM1) and pertuzumab, in patients with HER2-positive metastatic breast cancer (MBC).PATIENTS AND METHODS:
Patients with HER2-positive locally advanced breast cancer or MBC were treated with 3.6 mg/kg T-DM1 plus pertuzumab (840-mg loading dose, then 420 mg subsequently) once every 3 weeks. The primary efficacy end point was investigator-assessed objective response rate (ORR).RESULTS:
Sixty-four patients (43 patients in the second-line or greater setting [advanced MBC]; 21 patients in the first-line setting [first-line MBC]) were enrolled. Patients with advanced MBC had received trastuzumab and a median of six prior nonhormonal treatments for MBC; 86% of first-line MBC patients had received trastuzumab in the (neo)adjuvant setting. The ORR was 41% overall, 33% in patients with advanced MBC, and 57% in first-line patients. Median progression-free survival was 6.6, 5.5, and 7.7 months, respectively. The most common adverse events were fatigue (61%), nausea (50%), and diarrhea (39%). The most frequent grade ≥ 3 adverse events were thrombocytopenia (13%), fatigue (11%), and liver enzyme elevations (increased ALT: 9%; increased AST: 9%). One patient had left ventricular ejection fraction of less than 40% after study drug discontinuation. Exploratory biomarker analyses demonstrated that patients with above-median tumor HER2 mRNA levels had a numerically higher ORR than patients with below-median levels (44% v 33%, respectively).CONCLUSION:
T-DM1 and pertuzumab can be combined at full doses with no unexpected toxicities. The preliminary efficacy in patients in the first-line and advanced MBC settings warrants further investigation.Related: Breast Cancer
Kathy D. Miller, Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN; Reshma L. Mahtani, Sylvester Comprehensive Cancer Center, Miami, FL; Kathy S. Albain, Loyola University Chicago Stritch School of Medicine, Maywood, IL; Liang Fang, Glenn Michelson, Genentech, South San Franc...
Fulco I, Miot S, Haug MD, et al.Engineered autologous cartilage tissue for nasal reconstruction after tumour resection: an observational first-in-human trial.
Lancet. 2014; 384(9940):337-46 [PubMed
] Related Publications
Autologous native cartilage from the nasal septum, ear, or rib is the standard material for surgical reconstruction of the nasal alar lobule after two-layer excision of non-melanoma skin cancer. We assessed whether engineered autologous cartilage grafts allow safe and functional alar lobule restoration.METHODS:
In a first-in-human trial, we recruited five patients at the University Hospital Basel (Basel, Switzerland). To be eligible, patients had to be aged at least 18 years and have a two-layer defect (≥50% size of alar subunit) after excision of non-melanoma skin cancer on the alar lobule. Chondrocytes (isolated from a 6 mm cartilage biopsy sample from the nasal septum harvested under local anaesthesia during collection of tumour biopsy sample) were expanded, seeded, and cultured with autologous serum onto collagen type I and type III membranes in the course of 4 weeks. The resulting engineered cartilage grafts (25 mm × 25 mm × 2 mm) were shaped intra-operatively and implanted after tumour excision under paramedian forehead or nasolabial flaps, as in standard reconstruction with native cartilage. During flap refinement after 6 months, we took biopsy samples of repair tissues and histologically analysed them. The primary outcomes were safety and feasibility of the procedure, assessed 12 months after reconstruction. At least 1 year after implantation, when reconstruction is typically stabilised, we assessed patient satisfaction and functional outcomes (alar cutaneous sensibility, structural stability, and respiratory flow rate).FINDINGS:
Between Dec 13, 2010, and Feb 6, 2012, we enrolled two women and three men aged 76-88 years. All engineered grafts contained a mixed hyaline and fibrous cartilage matrix. 6 months after implantation, reconstructed tissues displayed fibromuscular fatty structures typical of the alar lobule. After 1 year, all patients were satisfied with the aesthetic and functional outcomes and no adverse events had been recorded. Cutaneous sensibility and structural stability of the reconstructed area were clinically satisfactory, with adequate respiratory function.INTERPRETATION:
Autologous nasal cartilage tissues can be engineered and clinically used for functional restoration of alar lobules. Engineered cartilage should now be assessed for other challenging facial reconstructions.FUNDING:
Foundation of the Department of Surgery, University Hospital Basel; and Krebsliga beider Basel.Related: Skin Cancer
Department of Surgery and Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland.
Croner RS, Geppert CI, Bader FG, et al.Molecular staging of lymph node-negative colon carcinomas by one-step nucleic acid amplification (OSNA) results in upstaging of a quarter of patients in a prospective, European, multicentre study.
Br J Cancer. 2014; 110(10):2544-50 [PubMed
] Article available free on PMC
after 13/05/2015 Related Publications
BACKGROUND: Current histopathological staging procedures in colon carcinomas depend on midline division of the lymph nodes with one section of haematoxylin & eosin (H&E) staining only. By this method, tumour deposits outside this transection line may be missed and could lead to understaging of a high-risk group of stage UICC II cases, which recurs in ∼20% of cases. A new diagnostic semiautomated system, one-step nucleic acid amplification (OSNA), detects cytokeratin (CK) 19 mRNA in lymph node metastases and enables the investigation of the whole lymph node. The objective of this study was to assess whether histopathological pN0 patients can be upstaged to stage UICC III by OSNA.
METHODS: Lymph nodes from patients who were classified as lymph node negative after standard histopathology (single (H&E) slice) were subjected to OSNA. A result revealing a CK19 mRNA copy number >250, which makes sure to detect mainly macrometastases and not isolated tumour cells (ITC) or micrometastases only, was regarded as positive for lymph node metastases based on previous threshold investigations.
RESULTS: In total, 1594 pN0 lymph nodes from 103 colon carcinomas (median number of lymph nodes per patient: 14, range: 1-46) were analysed with OSNA. Out of 103 pN0 patients, 26 had OSNA-positive lymph nodes, resulting in an upstaging rate of 25.2%. Among these were 6/37 (16.2%) stage UICC I and 20/66 (30.3%) stage UICC II patients. Overall, 38 lymph nodes were OSNA positive: 19 patients had one, 3 had two, 3 had three, and 1 patient had four OSNA-positive lymph nodes.
CONCLUSIONS: OSNA resulted in an upstaging of over 25% of initially histopathologically lymph node-negative patients. OSNA is a standardised, observer-independent technique, allowing the analysis of the whole lymph node. Therefore, sampling bias due to missing investigation of certain lymph node tissue can be avoided, which may lead to a more accurate staging.
Department of Surgery, University Hospital Erlangen, Erlangen, Germany.
Stockler MR, Hilpert F, Friedlander M, et al.Patient-reported outcome results from the open-label phase III AURELIA trial evaluating bevacizumab-containing therapy for platinum-resistant ovarian cancer.
J Clin Oncol. 2014; 32(13):1309-16 [PubMed
] Related Publications
To determine the effects of bevacizumab on patient-reported outcomes (PROs; secondary end point) in the AURELIA trial.PATIENTS AND METHODS:
Patients with platinum-resistant ovarian cancer were randomly assigned to chemotherapy alone (CT) or with bevacizumab (BEV-CT). PROs were assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Ovarian Cancer Module 28 (EORTC QLQ-OV28) and Functional Assessment of Cancer Therapy-Ovarian Cancer symptom index (FOSI) at baseline and every two or three cycles (8/9 weeks) until disease progression. The primary PRO hypothesis was that more patients receiving BEV-CT than CT would achieve at least a 15% (≥ 15-point) absolute improvement on the QLQ-OV28 abdominal/GI symptom subscale (items 31-36) at week 8/9. Patients with missing week 8/9 questionnaires were included as unimproved. Questionnaires from all assessments until disease progression were analyzed using mixed-model repeated-measures (MMRM) analysis. Sensitivity analyses were used to determine the effects of differing assumptions and methods for missing data.RESULTS:
Baseline questionnaires were available from 89% of 361 randomly assigned patients. More BEV-CT than CT patients achieved a ≥ 15% improvement in abdominal/GI symptoms at week 8/9 (primary PRO end point, 21.9% v 9.3%; difference, 12.7%; 95% CI, 4.4 to 20.9; P = .002). MMRM analysis covering all time points also favored BEV-CT (difference, 6.4 points; 95% CI, 1.3 to 11.6; P = .015). More BEV-CT than CT patients achieved ≥ 15% improvement in FOSI at week 8/9 (12.2% v 3.1%; difference, 9.0%; 95% CI, 2.9% to 15.2%; P = .003). Sensitivity analyses gave similar results and conclusions.CONCLUSION:
Bevacizumab increased the proportion of patients achieving a 15% improvement in patient-reported abdominal/GI symptoms during chemotherapy for platinum-resistant ovarian cancer.Related: Doxorubicin Ovarian Cancer Paclitaxel Topotecan Liposomal Doxorubicin Bevacizumab (Avastin)
Martin R. Stockler, Madeleine T. King, Chee Khoon Lee, The University of Sydney; Michael Friedlander, Prince of Wales Clinical School, University of New South Wales, Sydney, Australia; Felix Hilpert, Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) and Klinik für Gynäkologie und Ge...
Crawford ED, Shore ND, Moul JW, et al.Long-term tolerability and efficacy of degarelix: 5-year results from a phase III extension trial with a 1-arm crossover from leuprolide to degarelix.
Urology. 2014; 83(5):1122-8 [PubMed
] Related Publications
To demonstrate the safety and efficacy of up to 5 years of degarelix treatment and the effects of crossing over from leuprolide to degarelix in the extension phase of a phase III pivotal 1-year trial.METHODS:
Patients receiving degarelix who completed the 1-year trial continued on 80 mg (n = 125) or 160 mg (n = 126) maintenance doses. Patients who received leuprolide were rerandomized to degarelix 240/80 mg (n = 69) or 240/160 mg (n = 65). Safety and tolerability were assessed (primary end point), as well as testosterone and prostate-specific antigen levels and prostate-specific antigen progression-free survival (secondary end points).RESULTS:
Adverse event frequency was similar between both the groups. Adverse events included initial injection site reactions, hot flushes, and increased weight. Testosterone and prostate-specific antigen values during the extension study were similar to those seen during the 1-year trial in patients who continued on degarelix or crossed over from leuprolide. The prostate-specific antigen progression-free survival hazard rate was decreased significantly after the crossover in the leuprolide to degarelix group (from 0.20 to 0.09; P = .002), whereas in patients who continued on degarelix, the rate did not change significantly. In patients with baseline prostate-specific antigen >20 ng/mL, the same hazard rate change pattern was observed on crossover (from 0.38 to 0.19; P = .019).CONCLUSION:
Degarelix was well tolerated; no safety concerns were identified. The significant prostate-specific antigen progression-free survival benefit established for degarelix over leuprolide during year 1 remained consistent at 5 years.Related: Prostate Cancer
Department of Urologic Oncology, School of Medicine, University of Colorado Denver, Aurora, CO. Electronic address:
Gianni L, Eiermann W, Semiglazov V, et al.Neoadjuvant and adjuvant trastuzumab in patients with HER2-positive locally advanced breast cancer (NOAH): follow-up of a randomised controlled superiority trial with a parallel HER2-negative cohort.
Lancet Oncol. 2014; 15(6):640-7 [PubMed
] Related Publications
In our randomised, controlled, phase 3 trial NeOAdjuvant Herceptin (NOAH) trial in women with HER2-positive locally advanced or inflammatory breast cancer, neoadjuvant trastuzumab significantly improved pathological complete response rate and event-free survival. We report updated results from our primary analysis to establish the long-term benefit of trastuzumab-containing neoadjuvant therapy.METHODS:
We did this multicentre, open-label, randomised trial in women with HER2-positive locally advanced or inflammatory breast cancer. Participants were randomly assigned (1:1), by computer program with a minimisation technique, to receive neoadjuvant chemotherapy alone or with 1 year of trastuzumab (concurrently with neoadjuvant chemotherapy and continued after surgery). A parallel group with HER2-negative disease was included and received neoadjuvant chemotherapy alone. Our primary endpoint was event-free survival. Analysis was by intention to treat. This study is registered at www.controlled-trials.com, ISRCTN86043495.FINDINGS:
Between June 20, 2002, and Dec 12, 2005, we enrolled 235 patients with HER2-positive disease, of whom 118 received chemotherapy alone and 117 received chemotherapy plus trastuzumab. 99 additional patients with HER2-negative disease were included in the parallel cohort. After a median follow-up of 5.4 years (IQR 3.1-6.8) the event-free-survival benefit from the addition of trastuzumab to chemotherapy was maintained in patients with HER2-positive disease. 5 year event-free survival was 58% (95% CI 48-66) in patients in the trastuzumab group and 43% (34-52) in those in the chemotherapy group; the unadjusted hazard ratio (HR) for event-free survival between the two randomised HER2-positive treatment groups was 0.64 (95% CI 0.44-0.93; two-sided log-rank p=0.016). Event-free survival was strongly associated with pathological complete remission in patients given trastuzumab. Of the 68 patients with a pathological complete response (45 with trastuzumab and 23 with chemotherapy alone), the HR for event-free survival between those with and without trastuzumab was 0.29 (95% CI 0.11-0.78). During follow-up only four cardiovascular adverse events were regarded by the investigator to be drug-related (grade 2 lymphostasis and grade 2 lymphoedema, each in one patient in the trastuzumab group, and grade 2 thrombosis and grade 2 deep vein thrombosis, each in one patient in the chemotherapy-alone group).INTERPRETATION:
These results show a sustained benefit in event-free survival from trastuzumab-containing neoadjuvant therapy followed by adjuvant trastuzumab in patients with locally advanced or inflammatory breast cancer, and provide new insight into the association between pathological complete remission and long-term outcomes in HER2-positive disease.Related: Breast Cancer Trastuzumab (Herceptin)
San Raffaele Hospital, Milan, Italy. Electronic address:
Stilgenbauer S, Schnaiter A, Paschka P, et al.Gene mutations and treatment outcome in chronic lymphocytic leukemia: results from the CLL8 trial.
Blood. 2014; 123(21):3247-54 [PubMed
] Related Publications
Mutations in TP53, NOTCH1, and SF3B1 were analyzed in the CLL8 study evaluating first-line therapy with fludarabine and cyclophosphamide (FC) or FC with rituximab (FCR) among patients with untreated chronic lymphocytic leukemia (CLL). TP53, NOTCH1, and SF3B1 were mutated in 11.5%, 10.0%, and 18.4% of patients, respectively. NOTCH1(mut) and SF3B1(mut) virtually showed mutual exclusivity (0.6% concurrence), but TP53(mut) was frequently found in NOTCH1(mut) (16.1%) and in SF3B1(mut) (14.0%) patients. There were few significant associations with clinical and laboratory characteristics, but genetic markers had a strong influence on response and survival. In multivariable analyses, an independent prognostic impact was found for FCR, thymidine kinase (TK) ≥10 U/L, unmutated IGHV, 11q deletion, 17p deletion, TP53(mut), and SF3B1(mut) on progression-free survival; and for FCR, age ≥65 years, Eastern Cooperative Oncology Group performance status ≥1, β2-microglobulin ≥3.5 mg/L, TK ≥10 U/L, unmutated IGHV, 17p deletion, and TP53(mut) on overall survival. Notably, predictive marker analysis identified an interaction of NOTCH1 mutational status and treatment in that rituximab failed to improve response and survival in patients with NOTCH1(mut). In conclusion, TP53 and SF3B1 mutations appear among the strongest prognostic markers in CLL patients receiving current-standard first-line therapy. NOTCH1(mut) was identified as a predictive marker for decreased benefit from the addition of rituximab to FC. This study is registered at www.clinicaltrials.gov as #NCT00281918.Related: Cyclophosphamide Chronic Lymphocytic Leukemia (CLL) CLL - Molecular Biology TP53 Rituximab (Mabthera)
Department of Internal Medicine III, Ulm University, Ulm, Germany;
Zech CJ, Korpraphong P, Huppertz A, et al.Randomized multicentre trial of gadoxetic acid-enhanced MRI versus conventional MRI or CT in the staging of colorectal cancer liver metastases.
Br J Surg. 2014; 101(6):613-21 [PubMed
] Related Publications
This multicentre international randomized trial compared the impact of gadoxetic acid-enhanced magnetic resonance imaging (MRI), MRI with extracellular contrast medium (ECCM-MRI) and contrast-enhanced computed tomography (CE-CT) as a first-line imaging method in patients with suspected colorectal cancer liver metastases (CRCLM).METHODS:
Between October 2008 and September 2010, patients with suspected CRCLM were randomized to one of the three imaging modalities. The primary endpoint was the proportion of patients for whom further imaging after initial imaging was required for a confident diagnosis. Secondary variables included confidence in the therapeutic decision, intraoperative deviations from the initial imaging-based surgical plan as a result of additional operative findings, and diagnostic efficacy of the imaging modalities versus intraoperative and pathological extent of the disease.RESULTS:
A total of 360 patients were enrolled. Efficacy was analysed in 342 patients (118, 112 and 112 with gadoxetic acid-enhanced MRI, ECCM-MRI and CE-CT respectively as the initial imaging procedure). Further imaging was required in 0 of 118, 19 (17.0 per cent) of 112 and 44 (39.3 per cent) of 112 patients respectively (P < 0.001). Diagnostic confidence was high or very high in 98.3 per cent of patients for gadoxetic acid-enhanced MRI, 85.7 per cent for ECCM-MRI and 65.2 per cent for CE-CT. Surgical plans were changed during surgery in 28, 32 and 47 per cent of patients in the respective groups.CONCLUSION:
The diagnostic performance of gadoxetic acid-enhanced MRI was better than that of CE-CT and ECCM-MRI as the initial imaging modality. No further imaging was needed in the gadoxetic acid-enhanced MRI group and comparison of diagnostic efficacy parameters demonstrated the diagnostic superiority of gadoxetic acid-enhanced MRI.REGISTRATION NUMBER:
NCT00764621(http://clinicaltrials.gov); EudraCT number: 2008-000583-16 (https://eudract.ema.europa.eu/).Related: Colorectal (Bowel) Cancer
Institute of Clinical Radiology, University Hospital Munich - Grosshadern, Munich, and; Clinic of Radiology and Nuclear Medicine, University Hospital Basle, Basle, Switzerland.
Janssen S, Glanzmann C, Huber G, Studer GIndividualized IMRT treatment approach for cervical lymph node metastases of unknown primary.
Strahlenther Onkol. 2014; 190(4):386-93 [PubMed
] Related Publications
The goal of the present study was to evaluate the outcome of risk-adapted planning treatment volumes (PTVs) in patients with cervical lymph node metastases of unknown primary cancer (UPC) treated with intensity-modulated radiotherapy (IMRT).PATIENTS AND MATERIAL:
Between January 2006 and November 2012, 28 patients with cervical lymph node metastases of UPC were treated in our institution with IMRT either postoperatively (n = 20) or as definitive treatment (n = 8). Nodal involvement distributed as follows: N1 (n = 2), N2a (8), N2b (10), N2c (4), and N3 (4). Systemic therapy with cisplatin or cetuximab was added concomitantly in 20 of 28 patients (71 %). Radiotherapy using simultaneously integrated boost (SIB-IMRT) was carried out with 2.0 or 2.11 Gy single doses up to 66/70 Gy.RESULTS:
Mean/median follow-up was 31.6/30.5 months (range 3-78 months). In all, 15 of 28 patients were treated with unilateral SIB-IMRT (54 %). An elective PTV to the contralateral oropharynx and contralateral level II-III lymph nodes was carried out in 8 patients with PET-CT suspected but not histologically proven involvement, recurrences or former tumor of the oropharynx. More extended treatment fields were reserved for patients with N2c or bilaterally N3 status (n = 5). The 3-year overall survival, mucosal control, neck control and distant metastasis-free survival rates were 76, 100, 93, and 88 %, respectively. No patient suffered from a locoregional recurrence. Two patients treated with radiotherapy alone had persistent nodal disease. No grade II or higher late sequel has been observed.CONCLUSION:
Our single center approach to treat patients with cervical lymph node metastases of UPC with individualized, risk-adapted SIB-IMRT resulted in high locoregional tumor control and was well tolerated.Related: Cancer of Unknown Primary
Department of Radiation Oncology, University Hospital Zurich, Rämistr. 1000, 8091, Zurich, Switzerland.
Hillmen P, Gribben JG, Follows GA, et al.Rituximab plus chlorambucil as first-line treatment for chronic lymphocytic leukemia: Final analysis of an open-label phase II study.
J Clin Oncol. 2014; 32(12):1236-41 [PubMed
] Related Publications
Most patients with chronic lymphocytic leukemia (CLL) are elderly and/or have comorbidities that may make them ineligible for fludarabine-based treatment. For this population, chlorambucil monotherapy is an appropriate therapeutic option; however, response rates with chlorambucil are low, and more effective treatments are needed. This trial was designed to assess how the addition of rituximab to chlorambucil (R-chlorambucil) would affect safety and efficacy in patients with CLL.PATIENTS AND METHODS:
Patients with first-line CLL were treated with rituximab (375 mg/m(2) on day 1, cycle one, and 500 mg/m(2) thereafter) plus chlorambucil (10 mg/m(2)/d all cycles; day 1 through 7) for six 28-day cycles. For patients not achieving complete response (CR), six additional cycles of chlorambucil alone could be administered. The primary end point of the study was safety.RESULTS:
A total of 100 patients were treated with R-chlorambucil, with a median follow-up of 30 months. Median age of patients was 70 years (range, 43 to 86 years), with patients having a median of seven comorbidities. Hematologic toxicities accounted for most grade 3/4 adverse events reported, with neutropenia and lymphopenia both occurring in 41% of patients and leukopenia in 23%. Overall response rates were 84%, with CR achieved in 10% of patients. Median progression-free survival was 23.5 months; median overall survival was not reached.CONCLUSION:
These results compare favorably with previously published results for chlorambucil monotherapy, suggesting that the addition of rituximab to chlorambucil may improve efficacy with no unexpected adverse events. R-chlorambucil may improve outcome for patients who are ineligible for fludarabine-based treatments.Related: Chlorambucil Chronic Lymphocytic Leukemia (CLL) CLL - Molecular Biology Rituximab (Mabthera)
Peter Hillmen, Abraham Varghese, and Andy Rawstron, St James's Institute of Oncology; Dena Cohen, University of Leeds, Leeds; John G. Gribben, Barts and the London School of Medicine; Claire E. Dearden, Royal Marsden Hospital; Amit Nathwani, University College London, London; George A. Follows, Add...
Pujade-Lauraine E, Hilpert F, Weber B, et al.Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: The AURELIA open-label randomized phase III trial.
J Clin Oncol. 2014; 32(13):1302-8 [PubMed
] Related Publications
In platinum-resistant ovarian cancer (OC), single-agent chemotherapy is standard. Bevacizumab is active alone and in combination. AURELIA is the first randomized phase III trial to our knowledge combining bevacizumab with chemotherapy in platinum-resistant OC.PATIENTS AND METHODS:
Eligible patients had measurable/assessable OC that had progressed < 6 months after completing platinum-based therapy. Patients with refractory disease, history of bowel obstruction, or > two prior anticancer regimens were ineligible. After investigators selected chemotherapy (pegylated liposomal doxorubicin, weekly paclitaxel, or topotecan), patients were randomly assigned to single-agent chemotherapy alone or with bevacizumab (10 mg/kg every 2 weeks or 15 mg/kg every 3 weeks) until progression, unacceptable toxicity, or consent withdrawal. Crossover to single-agent bevacizumab was permitted after progression with chemotherapy alone. The primary end point was progression-free survival (PFS) by RECIST. Secondary end points included objective response rate (ORR), overall survival (OS), safety, and patient-reported outcomes.RESULTS:
The PFS hazard ratio (HR) after PFS events in 301 of 361 patients was 0.48 (95% CI, 0.38 to 0.60; unstratified log-rank P < .001). Median PFS was 3.4 months with chemotherapy alone versus 6.7 months with bevacizumab-containing therapy. RECIST ORR was 11.8% versus 27.3%, respectively (P = .001). The OS HR was 0.85 (95% CI, 0.66 to 1.08; P < .174; median OS, 13.3 v 16.6 months, respectively). Grade ≥ 2 hypertension and proteinuria were more common with bevacizumab. GI perforation occurred in 2.2% of bevacizumab-treated patients.CONCLUSION:
Adding bevacizumab to chemotherapy statistically significantly improved PFS and ORR; the OS trend was not significant. No new safety signals were observed.Related: Doxorubicin Ovarian Cancer Paclitaxel Topotecan Liposomal Doxorubicin Bevacizumab (Avastin)
Eric Pujade-Lauraine, Group d'Investigateurs Nationaux pour l'Etude des Cancers Ovariens (GINECO) and Université Paris Descartes, Assistance Publique-Hôpitaux de Paris, Paris; Béatrice Weber, GINECO and Centre Alexis Vautrin, Vandoeuvre-les-Nancy; Philippe Follana, GINECO and Centre ...
Donnez J, Vázquez F, Tomaszewski J, et al.Long-term treatment of uterine fibroids with ulipristal acetate ☆.
Fertil Steril. 2014; 101(6):1565-73.e1-18 [PubMed
] Related Publications
OBJECTIVE: To investigate the efficacy and safety of ulipristal acetate (UPA) for long-term treatment of symptomatic uterine fibroids.
DESIGN: Repeated intermittent open-label UPA courses, each followed by randomized double-blind norethisterone acetate (NETA) or placebo.
SETTING: European clinical gynecology centers.
PATIENT(S): Two hundred and nine women with symptomatic fibroids including heavy menstrual bleeding.
INTERVENTION(S): Patients received up to four 3-month courses of UPA 10 mg daily, immediately followed by 10-day double-blind treatment with NETA (10 mg daily) or placebo.
MAIN OUTCOME MEASURE(S): Amenorrhea, fibroid volume, endometrial histology.
RESULT(S): After the first UPA course, amenorrhea occurred in 79% of women, with median onset (from treatment start) of 4 days (interquartile range, 2-6 days). Median fibroid volume change was -45% (interquartile range, -66%; -25%). Amenorrhea rates were 89%, 88%, and 90% for the 131, 119, and 107 women who received treatment courses 2, 3, and 4, respectively. Median times to amenorrhea were 2, 3, and 3 days for treatment courses 2, 3, and 4, respectively. Median fibroid volume changes from baseline were -63%, -67%, and -72% after treatment courses 2, 3, and 4, respectively. All endometrial biopsies showed benign histology without hyperplasia; NETA did not affect fibroid volume or endometrial histology.
CONCLUSION(S): Repeated 3-month UPA courses effectively control bleeding and shrink fibroids in patients with symptomatic fibroids.
CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (www.clinicaltrials.gov) registration numbers NCT01156857 (PEARL III) and NCT01252069 (PEARL III extension).
Société de Recherche pour l'Infertilité, Brussels, Belgium. Electronic address:
Larkin J, Del Vecchio M, Ascierto PA, et al.Vemurafenib in patients with BRAF(V600) mutated metastatic melanoma: an open-label, multicentre, safety study.
Lancet Oncol. 2014; 15(4):436-44 [PubMed
] Related Publications
The orally available BRAF kinase inhibitor vemurafenib, compared with dacarbazine, shows improved response rates, progression-free survival (PFS), and overall survival in patients with metastatic melanoma that has a BRAF(V600) mutation. We assessed vemurafenib in patients with advanced metastatic melanoma with BRAF(V600) mutations who had few treatment options.METHODS:
In an open-label, multicentre study, patients with untreated or previously treated melanoma and a BRAF(V600) mutation received oral vemurafenib 960 mg twice a day. The primary endpoint was safety. All analyses were done on the safety population, which included all patients who received at least one dose of vemurafenib. This report is the third interim analysis of this study. This study is registered with ClinicalTrials.gov, number NCT01307397.FINDINGS:
Between March 1, 2011, and Jan 31, 2013, 3226 patients were enrolled in 44 countries. 3222 patients received at least one dose of vemurafenib (safety population). At data cutoff, 868 (27%) patients were on study treatment and 2354 (73%) had withdrawn, mainly because of disease progression. Common adverse events of all grades included rash (1592 [49%]), arthralgia (1259 [39%]), fatigue (1093 [34%]), photosensitivity reaction (994 [31%]), alopecia (826 [26%]), and nausea (628 [19%]). 1480 (46%) patients reported grade 3 or 4 adverse events, including cutaneous squamous cell carcinoma (389 [12%]), rash (155 [5%]), liver function abnormalities (165 [5%]), arthralgia (106 [3%]), and fatigue (93 [3%]). Grade 3 and 4 adverse events were reported more frequently in patients aged 75 years and older (n=257; 152 [59%, 95% CI 53-65] and ten [4%, 2-7], respectively) than in those younger than 75 years (n=2965; 1286 [43%, 42-45] and 82 [3%, 2-3], respectively).INTERPRETATION:
Vemurafenib safety in this diverse population of patients with BRAF(V600) mutated metastatic melanoma, who are more representative of routine clinical practice, was consistent with the safety profile shown in the pivotal trials of this drug.FUNDING:
F Hoffmann-La Roche.Related: Australia Canada BRAF gene Skin Cancer Vemurafenib (Zelboraf)
Royal Marsden Hospital NHS Foundation Trust, London, UK. Electronic address:
Motzer RJ, Porta C, Vogelzang NJ, et al.Dovitinib versus sorafenib for third-line targeted treatment of patients with metastatic renal cell carcinoma: an open-label, randomised phase 3 trial.
Lancet Oncol. 2014; 15(3):286-96 [PubMed
] Related Publications
An unmet medical need exists for patients with metastatic renal cell carcinoma who have progressed on VEGF-targeted and mTOR-inhibitor therapies. Fibroblast growth factor (FGF) pathway activation has been proposed as a mechanism of escape from VEGF-targeted therapies. Dovitinib is an oral tyrosine-kinase inhibitor that inhibits VEGF and FGF receptors. We therefore compared dovitinib with sorafenib as third-line targeted therapies in patients with metastatic renal cell carcinoma.METHODS:
In this multicentre phase 3 study, patients with clear cell metastatic renal cell carcinoma who received one previous VEGF-targeted therapy and one previous mTOR inhibitor were randomly assigned through an interactive voice and web response system to receive open-label dovitinib (500 mg orally according to a 5-days-on and 2-days-off schedule) or sorafenib (400 mg orally twice daily) in a 1:1 ratio. Randomisation was stratified by risk group and region. The primary endpoint was progression-free survival (PFS) assessed by masked central review. Efficacy was assessed in all patients who were randomly assigned and safety was assessed in patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT01223027.FINDINGS:
284 patients were randomly assigned to the dovitinib group and 286 to the sorafenib group. Median follow-up was 11·3 months (IQR 7·9-14·6). Median PFS was 3·7 months (95% CI 3·5-3·9) in the dovitinib group and 3·6 months (3·5-3·7) in the sorafenib group (hazard ratio 0·86, 95% CI 0·72-1·04; one-sided p=0·063). 280 patients in the dovitinib group and 284 in the sorafenib group received at least one dose of study drug. Common grade 3 or 4 adverse events included hypertriglyceridaemia (38 [14%]), fatigue (28 [10%]), hypertension (22 [8%]), and diarrhoea (20 [7%]) in the dovitinib group, and hypertension (47 [17%]), fatigue (24 [8%]), dyspnoea (21 [7%]), and palmar-plantar erythrodysaesthesia (18 [6%]) in the sorafenib group. The most common serious adverse event was dyspnoea (16 [6%] and 15 [5%] in the dovitinib and sorafenib groups, respectively).INTERPRETATION:
Dovitinib showed activity, but this was no better than that of sorafenib in patients with renal cell carcinoma who had progressed on previous VEGF-targeted therapies and mTOR inhibitors. This trial provides reference outcome data for future studies of targeted inhibitors in the third-line setting.FUNDING:
Novartis Pharmaceuticals Corporation.Related: Kidney Cancer VEGFA Sorafenib (Nexavar)
Memorial Sloan-Kettering Cancer Center, New York, NY, USA. Electronic address:
Chinot OL, Wick W, Mason W, et al.Bevacizumab plus radiotherapy-temozolomide for newly diagnosed glioblastoma.
N Engl J Med. 2014; 370(8):709-22 [PubMed
] Related Publications
Standard therapy for newly diagnosed glioblastoma is radiotherapy plus temozolomide. In this phase 3 study, we evaluated the effect of the addition of bevacizumab to radiotherapy-temozolomide for the treatment of newly diagnosed glioblastoma.METHODS:
We randomly assigned patients with supratentorial glioblastoma to receive intravenous bevacizumab (10 mg per kilogram of body weight every 2 weeks) or placebo, plus radiotherapy (2 Gy 5 days a week; maximum, 60 Gy) and oral temozolomide (75 mg per square meter of body-surface area per day) for 6 weeks. After a 28-day treatment break, maintenance bevacizumab (10 mg per kilogram intravenously every 2 weeks) or placebo, plus temozolomide (150 to 200 mg per square meter per day for 5 days), was continued for six 4-week cycles, followed by bevacizumab monotherapy (15 mg per kilogram intravenously every 3 weeks) or placebo until the disease progressed or unacceptable toxic effects developed. The coprimary end points were investigator-assessed progression-free survival and overall survival.RESULTS:
A total of 458 patients were assigned to the bevacizumab group, and 463 patients to the placebo group. The median progression-free survival was longer in the bevacizumab group than in the placebo group (10.6 months vs. 6.2 months; stratified hazard ratio for progression or death, 0.64; 95% confidence interval [CI], 0.55 to 0.74; P<0.001). The benefit with respect to progression-free survival was observed across subgroups. Overall survival did not differ significantly between groups (stratified hazard ratio for death, 0.88; 95% CI, 0.76 to 1.02; P=0.10). The respective overall survival rates with bevacizumab and placebo were 72.4% and 66.3% at 1 year (P=0.049) and 33.9% and 30.1% at 2 years (P=0.24). Baseline health-related quality of life and performance status were maintained longer in the bevacizumab group, and the glucocorticoid requirement was lower. More patients in the bevacizumab group than in the placebo group had grade 3 or higher adverse events (66.8% vs. 51.3%) and grade 3 or higher adverse events often associated with bevacizumab (32.5% vs. 15.8%).CONCLUSIONS:
The addition of bevacizumab to radiotherapy-temozolomide did not improve survival in patients with glioblastoma. Improved progression-free survival and maintenance of baseline quality of life and performance status were observed with bevacizumab; however, the rate of adverse events was higher with bevacizumab than with placebo. (Funded by F. Hoffmann-La Roche; ClinicalTrials.gov number, NCT00943826.).Related: Angiogenesis Inhibitors Dacarbazine Bevacizumab (Avastin) Temozolomide
From Aix-Marseille University, Assistance Publique-Hôpitaux de Marseille, Service de Neuro-Oncologie, Centre Hospitaliere Universitaire Timone, Marseille (O.L.C.), UFR de Santé, Médecine et Biologie Humaine, Bobigny (A.F.C.), and Assistance Publique-Hôpitaux de Paris (AP-HP), H&...
Maurer MJ, Ghesquières H, Jais JP, et al.Event-free survival at 24 months is a robust end point for disease-related outcome in diffuse large B-cell lymphoma treated with immunochemotherapy.
J Clin Oncol. 2014; 32(10):1066-73 [PubMed
] Article available free on PMC
after 01/04/2015 Related Publications
Studies of diffuse large B-cell lymphoma (DLBCL) are typically evaluated by using a time-to-event approach with relapse, re-treatment, and death commonly used as the events. We evaluated the timing and type of events in newly diagnosed DLBCL and compared patient outcome with reference population data.PATIENTS AND METHODS:
Patients with newly diagnosed DLBCL treated with immunochemotherapy were prospectively enrolled onto the University of Iowa/Mayo Clinic Specialized Program of Research Excellence Molecular Epidemiology Resource (MER) and the North Central Cancer Treatment Group NCCTG-N0489 clinical trial from 2002 to 2009. Patient outcomes were evaluated at diagnosis and in the subsets of patients achieving event-free status at 12 months (EFS12) and 24 months (EFS24) from diagnosis. Overall survival was compared with age- and sex-matched population data. Results were replicated in an external validation cohort from the Groupe d'Etude des Lymphomes de l'Adulte (GELA) Lymphome Non Hodgkinien 2003 (LNH2003) program and a registry based in Lyon, France.RESULTS:
In all, 767 patients with newly diagnosed DLBCL who had a median age of 63 years were enrolled onto the MER and NCCTG studies. At a median follow-up of 60 months (range, 8 to 116 months), 299 patients had an event and 210 patients had died. Patients achieving EFS24 had an overall survival equivalent to that of the age- and sex-matched general population (standardized mortality ratio [SMR], 1.18; P = .25). This result was confirmed in 820 patients from the GELA study and registry in Lyon (SMR, 1.09; P = .71). Simulation studies showed that EFS24 has comparable power to continuous EFS when evaluating clinical trials in DLBCL.CONCLUSION:
Patients with DLBCL who achieve EFS24 have a subsequent overall survival equivalent to that of the age- and sex-matched general population. EFS24 will be useful in patient counseling and should be considered as an end point for future studies of newly diagnosed DLBCL.Related: Rituximab (Mabthera)
Matthew J. Maurer, Hervé Ghesquières, Thomas E. Witzig, Carrie A. Thompson, Ivana N. Micallef, William R. Macon, Paul J. Kurtin, Cristine Allmer, Susan L. Slager, Thomas M. Habermann, and James R. Cerhan, Mayo Clinic, Rochester, MN; Hervé Ghesquières and Emmanuelle Nicolas-Virel...
Davies A, Merli F, Mihaljevic B, et al.Pharmacokinetics and safety of subcutaneous rituximab in follicular lymphoma (SABRINA): stage 1 analysis of a randomised phase 3 study.
Lancet Oncol. 2014; 15(3):343-52 [PubMed
] Related Publications
Intravenous rituximab is a mainstay of treatment for follicular lymphoma. A subcutaneous formulation that achieves equivalent rituximab serum concentrations might improve convenience and save health-care resources without sacrificing clinical activity. We aimed to assess pharmacokinetic non-inferiority of 3 week cycles of fixed-dose subcutaneous rituximab versus standard intravenous rituximab.METHODS:
In our two-stage, randomised, open-label, phase 3 trial, we enrolled patients with previously untreated grade 1-3a, CD20-positive follicular lymphoma at 67 centres in 23 countries. In stage 1, we randomly allocated patients 1:1 with the Pocock and Simon algorithm to intravenous rituximab (375 mg/m(2)) or fixed-dose subcutaneous rituximab (1400 mg), stratified by induction chemotherapy regimen (cyclophosphamide, doxorubicin, vincristine, prednisone or cyclophosphamide, vincristine, prednisone), Follicular Lymphoma International Prognostic Index score, and region. After randomisation, patients received one induction dose of intravenous rituximab in cycle 1 and then allocated treatment for cycles 2-8. Patients with a complete or partial response following induction therapy continued intravenous or subcutaneous rituximab as maintenance every 8 weeks. The primary endpoint was the ratio of observed rituximab serum trough concentrations (Ctrough) between groups at cycle 7 (before cycle 8 dosing) of induction treatment in a per-protocol population. Patients were analysed as treated for safety endpoints. Stage 2 follow-up is ongoing and is fully accrued. This study is registered with ClinicalTrials.gov, number NCT01200758.FINDINGS:
Between Feb 4, 2010, and Oct 21, 2011, we enrolled 127 patients. Pharmacokinetic data were available for 48 (75%) of 64 patients randomly allocated intravenous rituximab and 54 (86%) of 63 patients randomly allocated subcutaneous rituximab. Geometric mean Ctrough was 83·13 μg/mL in the intravenous group and 134·58 μg/mL in the subcutaneous group (ratio 1·62, 90% CI 1·36-1·94), showing non-inferiority of subcutaneous rituximab. 57 (88%) of 65 patients in the intravenous rituximab safety population had adverse events (30 [46%] grade ≥3), as did 57 (92%) of 62 patients in the subcutaneous rituximab safety population (29 [47%] grade ≥3). The most common grade 3 or worse adverse event in both groups was neutropenia (14 [22%] patients in the intravenous group and 16 [26%] patients in the subcutaneous group). Adverse events related to administration were mostly grade 1-2 and occurred in 21 (32%) patients in the intravenous group and 31 (50%) patients in the subcutaneous group.INTERPRETATION:
Stage 1 data show that the pharmacokinetic profile of subcutaneous rituximab was non-inferior to intravenous rituximab and was not associated with new safety concerns. Stage 2 will provide data for efficacy and safety of the subcutaneous administration.FUNDING:
F Hoffmann-La Roche.Related: Rituximab (Mabthera)
Cancer Research UK Centre, University of Southampton Faculty of Medicine, Southampton, UK. Electronic address:
Cosson VF, Ng VW, Lehle M, Lum BLPopulation pharmacokinetics and exposure-response analyses of trastuzumab in patients with advanced gastric or gastroesophageal junction cancer.
Cancer Chemother Pharmacol. 2014; 73(4):737-47 [PubMed
] Related Publications
The aim of this study was to characterize trastuzumab population pharmacokinetics (PKs) in patients with human epidermal growth factor receptor 2-positive advanced gastric or gastroesophageal junction cancer and the relationship of trastuzumab PK with patient response.METHODS:
A nonlinear mixed effects PK model was built using data from the ToGA study. Patients were randomized to intravenous trastuzumab plus chemotherapy or chemotherapy alone. The influence of demographic, laboratory, and disease characteristics on PK parameters was assessed. An exploratory exposure-response analysis compared various PK parameters at steady state with best overall tumor response and overall survival (OS).RESULTS:
Trastuzumab PK was best described by a two-compartment model with parallel linear and nonlinear (Michaelis-Menten) elimination from the central compartment. Total clearance (and half-life) of trastuzumab was concentration-dependent. Body weight, prior gastrectomy, and serum albumin had the greatest influence on trastuzumab PK; increasing weight and decreasing albumin levels were associated with increased clearance, while prior gastrectomy correlated with decreased clearance. Median values for AUC, Cmax, and Cmin were lower in patients with progressive disease (PD) than other response categories, although the 1.5 interquartile ranges overlapped. Patients with the lowest Cmin had the highest PD rate and a shorter OS.CONCLUSIONS:
In the advanced gastric cancer population, trastuzumab PK was best described by a two-compartment model with parallel linear and nonlinear elimination. Predicted PK exposure was lower than previously reported for breast cancer. Patients with the lowest Cmin had a shorter OS and the highest PD rate, but a distinct correlation was not observed for tumor response.Related: Cisplatin Cancer of the Esophagus Esophageal Cancer Fluorouracil Stomach Cancer Gastric Cancer Capecitabine Trastuzumab (Herceptin)
F. Hoffmann-La Roche Ltd., Postfach, 4070, Basel, Switzerland,
McArthur GA, Chapman PB, Robert C, et al.Safety and efficacy of vemurafenib in BRAF(V600E) and BRAF(V600K) mutation-positive melanoma (BRIM-3): extended follow-up of a phase 3, randomised, open-label study.
Lancet Oncol. 2014; 15(3):323-32 [PubMed
] Related Publications
In the BRIM-3 trial, vemurafenib was associated with risk reduction versus dacarbazine of both death and progression in patients with advanced BRAF(V600) mutation-positive melanoma. We present an extended follow-up analysis of the total population and in the BRAF(V600E) and BRAF(V600K) mutation subgroups.METHODS:
Patients older than 18 years, with treatment-naive metastatic melanoma and whose tumour tissue was positive for BRAF(V600) mutations were eligible. Patients also had to have a life expectancy of at least 3 months, an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and adequate haematological, hepatic, and renal function. Patients were randomly assigned by interactive voice recognition system to receive either vemurafenib (960 mg orally twice daily) or dacarbazine (1000 mg/m(2) of body surface area intravenously every 3 weeks). Coprimary endpoints were overall survival and progression-free survival, analysed in the intention-to-treat population (n=675), with data censored at crossover. A sensitivity analysis was done. This trial is registered with ClinicalTrials.gov, NCT01006980.FINDINGS:
675 eligible patients were enrolled from 104 centres in 12 countries between Jan 4, 2010, and Dec 16, 2010. 337 patients were randomly assigned to receive vemurafenib and 338 to receive dacarbazine. Median follow-up was 12·5 months (IQR 7·7-16·0) on vemurafenib and 9·5 months (3·1-14·7) on dacarbazine. 83 (25%) of the 338 patients initially randomly assigned to dacarbazine crossed over from dacarbazine to vemurafenib. Median overall survival was significantly longer in the vemurafenib group than in the dacarbazine group (13·6 months [95% CI 12·0-15·2] vs 9·7 months [7·9-12·8]; hazard ratio [HR] 0·70 [95% CI 0·57-0·87]; p=0·0008), as was median progression-free survival (6·9 months [95% CI 6·1-7·0] vs 1·6 months [1·6-2·1]; HR 0·38 [95% CI 0·32-0·46]; p<0·0001). For the 598 (91%) patients with BRAF(V600E) disease, median overall survival in the vemurafenib group was 13·3 months (95% CI 11·9-14·9) compared with 10·0 months (8·0-14·0) in the dacarbazine group (HR 0·75 [95% CI 0·60-0·93]; p=0·0085); median progression-free survival was 6·9 months (95% CI 6·2-7·0) and 1·6 months (1·6-2·1), respectively (HR 0·39 [95% CI 0·33-0·47]; p<0·0001). For the 57 (9%) patients with BRAF(V600K) disease, median overall survival in the vemurafenib group was 14·5 months (95% CI 11·2-not estimable) compared with 7·6 months (6·1-16·6) in the dacarbazine group (HR 0·43 [95% CI 0·21-0·90]; p=0·024); median progression-free survival was 5·9 months (95% CI 4·4-9·0) and 1·7 months (1·4-2·9), respectively (HR 0·30 [95% CI 0·16-0·56]; p<0·0001). The most frequent grade 3-4 events were cutaneous squamous-cell carcinoma (65 [19%] of 337 patients) and keratoacanthomas (34 [10%]), rash (30 [9%]), and abnormal liver function tests (38 [11%]) in the vemurafenib group and neutropenia (26 [9%] of 287 patients) in the dacarbazine group. Eight (2%) patients in the vemurafenib group and seven (2%) in the dacarbazine group had grade 5 events.INTERPRETATION:
Inhibition of BRAF with vemurafenib improves survival in patients with the most common BRAF(V600E) mutation and in patients with the less common BRAF(V600K) mutation.FUNDING:
F Hoffmann-La Roche-Genentech.Related: Dacarbazine Melanoma BRAF gene Vemurafenib (Zelboraf)
Peter MacCallum Cancer Centre, East Melbourne, VIC, Australia. Electronic address:
Gambacorti Passerini C, Farina F, Stasia A, et al.Crizotinib in advanced, chemoresistant anaplastic lymphoma kinase-positive lymphoma patients.
J Natl Cancer Inst. 2014; 106(2):djt378 [PubMed
] Related Publications
Anaplastic lymphoma kinase (ALK)-positive lymphomas respond to chemotherapy, but relapses, which bear a poor prognosis, occur. Crizotinib inhibits ALK in vitro and in vivo and was administered as monotherapy to 11 ALK+ lymphoma patients who were resistant/refractory to cytotoxic therapy. The overall response rate was 10 of 11 (90.9%; 95% confidence interval [CI] = 58.7% to 99.8%). Disease status at the latest follow-up is as follows: four patients are in complete response (CR) (months >21, >30, >35, >40) under continuous crizotinib administration; 4 patients had progression of disease (months 1, 2, 2, 2); 1 patient obtained CR on crizotinib, received an allogeneic bone marrow transplant, and is in CR; 2 patients (treated before and/or after allogeneic bone marrow transplant) obtained and are still in CR but they have stopped crizotinib. Overall and progression-free survival rates at 2 years are 72.7% (95% CI = 39.1% to 94.0%) and 63.7% (95% CI = 30.8% to 89.1%), respectively. ALK mutations conferring resistance to crizotinib in vitro could be identified in relapsed patients. Crizotinib exerted a potent antitumor activity with durable responses in advanced, heavily pretreated ALK+ lymphoma patients, with a benign safety profile.Related: FISH Non Hodgkin's Lymphoma Crizotinib (Xalkori)
Affiliations of authors: Department of Health Sciences, University Milano Bicocca, Monza, Italy (CGP, FF, AS, SR, MC, LMo, CM, LA, RP); Hematology Unit (CGP) and Nuclear Medicine and PET Unit (CM, LG), San Gerardo Hospital, Monza, Italy; M Tettamanti Research Center, Pediatric Clinic University of ...
Bosset JF, Calais G, Mineur L, et al.Fluorouracil-based adjuvant chemotherapy after preoperative chemoradiotherapy in rectal cancer: long-term results of the EORTC 22921 randomised study.
Lancet Oncol. 2014; 15(2):184-90 [PubMed
] Related Publications
EORTC trial 22921 examined the addition of preoperative or postoperative chemotherapy to preoperative radiotherapy in patients with rectal cancer. After a median follow-up of 5 years, chemotherapy-irrespective of timing-significantly improved local control. Adjuvant chemotherapy did not improve survival, but the Kaplan-Meier curves diverged, suggesting possible delayed benefit. Here, we report the updated long-term results.METHODS:
We randomly assigned patients with clinical stage T3 or T4 resectable rectal cancer to receive preoperative radiotherapy with or without concomitant chemotherapy before surgery followed by either adjuvant chemotherapy or surveillance. Randomisation was done using minimisation with factors of institution, sex, T stage, and distance from the tumour to the anal verge. Study coordinators, clinicians, and patients were aware of assignment. Radiotherapy consisted of 45 Gy to the posterior pelvis in 25 fractions of 1·8 Gy over 5 weeks. Each course of chemotherapy consisted of fluorouracil (350 mg/m(2) per day intravenous bolus) and folinic acid (leucovorin; 20 mg/m(2) per day intravenous bolus). For preoperative chemotherapy, two courses were given (during weeks 1 and 5 of radiotherapy). Adjuvant chemotherapy was given in four cycles, every 3 weeks. The primary endpoint was overall survival. This analysis was done by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00002523.FINDINGS:
1011 patients were randomly assigned to treatment between April, 1993, and March, 2003 (252 to preoperative radiotherapy and 253 to each of the other three groups). After a median follow-up of 10·4 years (IQR 7·8-13·1), 10-year overall survival was 49·4% (95% CI 44·6-54·1) for the preoperative radiotherapy group and 50·7% (45·9-55·2) for the preoperative radiotherapy and chemotherapy group (HR 0·99, 95% CI 0·83-1·18; p=0·91). 10-year overall survival was 51·8% (95% CI 47·0-56·4) for the adjuvant chemotherapy group and 48·4% (43·6-53·0) for the surveillance group (HR 0·91, 95% CI 0·77-1·09, p=0·32). 10-year disease-free survival was 44·2% (95% CI 39·5-48·8) for the preoperative radiotherapy group and 46·4% (41·7-50·9) for the preoperative radiotherapy and chemotherapy group (HR 0·93, 95% CI 0·79-1·10; p=0·38). 10-year disease-free survival was 47·0% (95% CI 42·2-51·6) for the adjuvant chemotherapy group and 43·7% (39·1-48·2) for the surveillance group (HR 0·91, 95% CI 0·77-1·08, p=0·29). At 10 years, cumulative incidence of local relapse was 22·4% (95% CI 17·1-27·6) with radiotherapy alone, 11·8% (7·8-15·8) with neoadjuvant radiotherapy and chemotherapy, 14·5% (10·1-18·9) with radiotherapy and adjuvant chemotherapy and 11·7% (7·7-15·6) with both adjuvant and neoadjuvant chemotherapy (p=0·0017). There was no difference in cumulative incidence of distant metastases (p=0·52). The frequency of long-term side-effects did not differ between the four groups (p=0·22).INTERPRETATION:
Adjuvant fluorouracil-based chemotherapy after preoperative radiotherapy (with or without chemotherapy) does not affect disease-free survival or overall survival. Our trial does not support the current practice of adjuvant chemotherapy after preoperative radiotherapy with or without chemotherapy. New treatment strategies incorporating neoadjuvant chemotherapy are required.FUNDING:
EORTC, US National Cancer Institute, Programme Hospitalier de Recherche Clinique, Ligue contre le Cancer Comité du Doubs.Related: Fluorouracil Leucovorin
Department of Radiation Oncology, Besançon University Hospital J Minjoz, Besançon, France. Electronic address:
Aebi S, Gelber S, Anderson SJ, et al.Chemotherapy for isolated locoregional recurrence of breast cancer (CALOR): a randomised trial.
Lancet Oncol. 2014; 15(2):156-63 [PubMed
] Article available free on PMC
after 01/02/2015 Related Publications
Patients with isolated locoregional recurrences (ILRR) of breast cancer have a high risk of distant metastasis and death from breast cancer. We aimed to establish whether adjuvant chemotherapy improves the outcome of such patients.METHODS:
The CALOR trial was a pragmatic, open-label, randomised trial that accrued patients with histologically proven and completely excised ILRR after unilateral breast cancer who had undergone a mastectomy or lumpectomy with clear surgical margins. Eligible patients were enrolled from hospitals worldwide and were centrally randomised (1:1) to chemotherapy (type selected by the investigator; multidrug for at least four courses recommended) or no chemotherapy, using permuted blocks, and stratified by previous chemotherapy, oestrogen-receptor and progesterone-receptor status, and location of ILRR. Patients with oestrogen-receptor-positive ILRR received adjuvant endocrine therapy, radiation therapy was mandated for patients with microscopically involved surgical margins, and anti-HER2 therapy was optional. The primary endpoint was disease-free survival. All analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00074152.FINDINGS:
From Aug 22, 2003, to Jan 31, 2010, 85 patients were randomly assigned to receive chemotherapy and 77 were assigned to no chemotherapy. At a median follow-up of 4·9 years (IQR 3·6-6 ·0), 24 (28%) patients had disease-free survival events in the chemotherapy group compared with 34 (44%) in the no chemotherapy group. 5-year disease-free survival was 69% (95% CI 56-79) with chemotherapy versus 57% (44-67) without chemotherapy (hazard ratio 0·59 [95% CI 0·35-0·99]; p=0·046). Adjuvant chemotherapy was significantly more effective for women with oestrogen-receptor-negative ILRR (pinteraction=0·046), but analyses of disease-free survival according to the oestrogen-receptor status of the primary tumour were not statistically significant (pinteraction=0·43). Of the 81 patients who received chemotherapy, 12 (15%) had serious adverse events. The most common adverse events were neutropenia, febrile neutropenia, and intestinal infection.INTERPRETATION:
Adjuvant chemotherapy should be recommended for patients with completely resected ILRR of breast cancer, especially if the recurrence is oestrogen-receptor negative.FUNDING:
US Department of Health and Human Services, Swiss Group for Clinical Cancer Research (SAKK), Frontier Science and Technology Research Foundation, Australian and New Zealand Breast Cancer Trials Group, Swedish Cancer Society, Oncosuisse, Cancer Association of South Africa, Foundation for Clinical Research of Eastern Switzerland (OSKK), Grupo Español de Investigación en Cáncer de Mama (GEICAM), and the Dutch Breast Cancer Trialists' Group (BOOG).Related: Australia Breast Cancer
Luzerner Kantonsspital, Lucerne, Switzerland; University of Berne, Berne, Switzerland; Swiss Group for Clinical Cancer Research (SAKK), Berne, Switzerland. Electronic address:
Colao A, Bronstein MD, Freda P, et al.Pasireotide versus octreotide in acromegaly: a head-to-head superiority study.
J Clin Endocrinol Metab. 2014; 99(3):791-9 [PubMed
] Article available free on PMC
after 01/02/2015 Related Publications
CONTEXT: Biochemical control reduces morbidity and increases life expectancy in patients with acromegaly. With current medical therapies, including the gold standard octreotide long-acting-release (LAR), many patients do not achieve biochemical control.
OBJECTIVE: Our objective was to demonstrate the superiority of pasireotide LAR over octreotide LAR in medically naive patients with acromegaly.
DESIGN AND SETTING: We conducted a prospective, randomized, double-blind study at 84 sites in 27 countries.
PATIENTS: A total of 358 patients with medically naive acromegaly (GH >5 μg/L or GH nadir ≥1 μg/L after an oral glucose tolerance test (OGTT) and IGF-1 above the upper limit of normal) were enrolled. Patients either had previous pituitary surgery but no medical treatment or were de novo with a visible pituitary adenoma on magnetic resonance imaging.
INTERVENTIONS: Patients received pasireotide LAR 40 mg/28 days (n = 176) or octreotide LAR 20 mg/28 days (n = 182) for 12 months. At months 3 and 7, titration to pasireotide LAR 60 mg or octreotide LAR 30 mg was permitted, but not mandatory, if GH ≥2.5μg/L and/or IGF-1 was above the upper limit of normal.
MAIN OUTCOME MEASURE: The main outcome measure was the proportion of patients in each treatment arm with biochemical control (GH <2.5 μg/L and normal IGF-1) at month 12.
RESULTS: Biochemical control was achieved by significantly more pasireotide LAR patients than octreotide LAR patients (31.3% vs 19.2%; P = .007; 35.8% vs 20.9% when including patients with IGF-1 below the lower normal limit). In pasireotide LAR and octreotide LAR patients, respectively, 38.6% and 23.6% (P = .002) achieved normal IGF-1, and 48.3% and 51.6% achieved GH <2.5 μg/L. 31.0% of pasireotide LAR and 22.2% of octreotide LAR patients who did not achieve biochemical control did not receive the recommended dose increase. Hyperglycemia-related adverse events were more common with pasireotide LAR (57.3% vs 21.7%).
CONCLUSIONS: Pasireotide LAR demonstrated superior efficacy over octreotide LAR and is a viable new treatment option for acromegaly.
Dipartimento di Medicina Clinica e Chirurgia (A.C.), Università Federico II di Napoli, 80131 Naples, Italy; Neuroendocrine Unit (M.D.B.), Division of Endocrinology and Metabolism, University of São Paulo Medical School, 3858-Jardim Paulista, São Paulo, Brazil; Department of Medicine ...
Giovacchini G, Picchio M, Garcia-Parra R, et al.11C-choline PET/CT predicts prostate cancer-specific survival in patients with biochemical failure during androgen-deprivation therapy.
J Nucl Med. 2014; 55(2):233-41 [PubMed
] Related Publications
Several studies have shown that (11)C-choline PET/CT may be useful for restaging prostate cancer (PCa) patients with biochemical failure after radical prostatectomy. However, validation of (11)C-choline PET/CT findings scarcely relied on histologic findings, and prognostic implications of (11)C-choline PET/CT are currently unknown. The aim of this study was to assess whether (11)C-choline PET/CT predicts survival in PCa patients.METHODS:
This retrospective study included 195 PCa patients treated with radical prostatectomy who underwent (11)C-choline PET/CT from December 1, 2004, to July 31, 2007, due to biochemical failure (prostate-specific antigen > 0.2 mg/mL) during androgen-deprivation therapy. PCa-specific survival was computed as the interval from radical prostatectomy to PCa-specific death.RESULTS:
The median interval after radical prostatectomy was 8.9 y (95% confidence interval [CI], 1.7-18.9 y). The median follow-up after (11)C-choline PET/CT was 4.5 y (95% CI, 0.4-8.5 y). (11)C-choline PET/CT results were positive in 57% of patients. The median PCa-specific survival was 16.4 y (95% CI, 14.0-18.8 y) in patients with negative (11)C-choline PET/CT results and 11.2 y (95% CI, 9.8-12.6 y) in patients with positive (11)C-choline PET/CT results (log-rank: χ(2) = 19.3, P < 0001). At multivariate analysis, statistical significance was obtained for (11)C-choline PET/CT (hazard ratio, 2.53; 95% CI, 1.41-4.53; P = 0.002), prostate-specific antigen (hazard ratio, 1.03; 95% CI, 1.00-1.05; P = 0.037), and Gleason score (>7: hazard ratio, 2.49; 95% CI, 1.25-4.95; P = 0.009). Patients with pathologic (11)C-choline uptake in the prostatic bed or in pelvic or retroperitoneal lymph nodes had longer PCa-specific survival (median, 12.1 y; 95% CI, 10.5-13.7 y) in comparison to patients with pathologic tracer uptake in the skeleton (median, 9.9 y; 95% CI, 6.8-13.1 y) (log-rank: χ(2) = 6.5, P = 0.010). Two internally validated nomograms predicted 10- and 15-y PCa-specific survival probability with an accuracy of 76% and 74%, respectively. In an ancillary analysis, we also showed that (11)C-choline PET/CT predicts PCa-specific survival after PET/CT, with similar statistical power.CONCLUSION:
(11)C-choline PET/CT predicts PCa-specific survival in PCa patients treated with radical prostatectomy who develop biochemical failure during androgen-deprivation therapy. If independent or multicenter confirmation of these findings is obtained, (11)C-choline PET/CT might be more widely used in the follow-up of PCa patients for tailoring salvage therapy.Related: Prostate Cancer
Department of Radiology, Stadtspital Triemli, Zurich, Switzerland.
Goede V, Fischer K, Busch R, et al.Obinutuzumab plus chlorambucil in patients with CLL and coexisting conditions.
N Engl J Med. 2014; 370(12):1101-10 [PubMed
] Related Publications
The monoclonal anti-CD20 antibody rituximab, combined with chemotherapeutic agents, has been shown to prolong overall survival in physically fit patients with previously untreated chronic lymphocytic leukemia (CLL) but not in those with coexisting conditions. We investigated the benefit of the type 2, glycoengineered antibody obinutuzumab (also known as GA101) as compared with that of rituximab, each combined with chlorambucil, in patients with previously untreated CLL and coexisting conditions.METHODS:
We randomly assigned 781 patients with previously untreated CLL and a score higher than 6 on the Cumulative Illness Rating Scale (CIRS) (range, 0 to 56, with higher scores indicating worse health status) or an estimated creatinine clearance of 30 to 69 ml per minute to receive chlorambucil, obinutuzumab plus chlorambucil, or rituximab plus chlorambucil. The primary end point was investigator-assessed progression-free survival.RESULTS:
The patients had a median age of 73 years, creatinine clearance of 62 ml per minute, and CIRS score of 8 at baseline. Treatment with obinutuzumab-chlorambucil or rituximab-chlorambucil, as compared with chlorambucil monotherapy, increased response rates and prolonged progression-free survival (median progression-free survival, 26.7 months with obinutuzumab-chlorambucil vs. 11.1 months with chlorambucil alone; hazard ratio for progression or death, 0.18; 95% confidence interval [CI], 0.13 to 0.24; P<0.001; and 16.3 months with rituximab-chlorambucil vs. 11.1 months with chlorambucil alone; hazard ratio, 0.44; 95% CI, 0.34 to 0.57; P<0.001). Treatment with obinutuzumab-chlorambucil, as compared with chlorambucil alone, prolonged overall survival (hazard ratio for death, 0.41; 95% CI, 0.23 to 0.74; P=0.002). Treatment with obinutuzumab-chlorambucil, as compared with rituximab-chlorambucil, resulted in prolongation of progression-free survival (hazard ratio, 0.39; 95% CI, 0.31 to 0.49; P<0.001) and higher rates of complete response (20.7% vs. 7.0%) and molecular response. Infusion-related reactions and neutropenia were more common with obinutuzumab-chlorambucil than with rituximab-chlorambucil, but the risk of infection was not increased.CONCLUSIONS:
Combining an anti-CD20 antibody with chemotherapy improved outcomes in patients with CLL and coexisting conditions. In this patient population, obinutuzumab was superior to rituximab when each was combined with chlorambucil. (Funded by F. Hoffmann-La Roche; ClinicalTrials.gov number, NCT01010061.).Related: Chlorambucil Chronic Lymphocytic Leukemia (CLL) CLL - Molecular Biology Rituximab (Mabthera) Obinutuzumab (Gazyva)
From the German CLL Study Group, Department I of Internal Medicine, Center of Integrated Oncology Cologne-Bonn, University Hospital Cologne, Cologne (V.G., K.F., A.E., B.E., C.M.W., K.-A.K., M.H.), the Department for Geriatric Medicine and Research, St. Marien Hospital and University of Cologne, Co...
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