The Experts below are selected from a list of 321 Experts worldwide ranked by ideXlab platform
Caroline Robert - One of the best experts on this subject based on the ideXlab platform.
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Vemurafenib in patients with BRAFV600 mutation-positive metastatic melanoma: final overall survival results of the randomized BRIM-3 study
Annals of Oncology, 2017Co-Authors: Paul B. Chapman, Antoni Ribas, Caroline Robert, James Larkin, John B. A. G. Haanen, David Hogg, Omid Hamid, P.a. Ascierto, Alessandro Testori, Paul LoriganAbstract:Background: The BRIM-3 trial showed improved progression-free survival (PFS) and overall survival (OS) for vemurafenib compared with Dacarbazine in treatment-naive patients with BRAFV600 mutation-positive metastatic melanoma. We present final OS data from BRIM-3. Patients and methods: Patients were randomly assigned in a 1 : 1 ratio to receive vemurafenib (960 mg twice daily) or Dacarbazine (1000 mg/m2 every 3 weeks). OS and PFS were co-primary end points. OS was assessed in the intention-to-treat population, with and without censoring of data for Dacarbazine patients who crossed over to vemurafenib. Results: Between 4 January 2010 and 16 December 2010, a total of 675 patients were randomized to vemurafenib (n = 337) or Dacarbazine (n = 338, of whom 84 crossed over to vemurafenib). At the time of database lock (14 August 2015), median OS, censored at crossover, was significantly longer for vemurafenib than for Dacarbazine {13.6 months [95% confidence interval (CI) 12.0-15.4] versus 9.7 months [95% CI 7.9-12.8; hazard ratio (HR) 0.81 [95% CI 0.67-0.98]; P = 0.03}, as was median OS without censoring at crossover [13.6 months (95% CI 12.0-15.4) versus 10.3 months (95% CI 9.1-12.8); HR 0.81 (95% CI 0.68-0.96); P = 0.01]. Kaplan-Meier estimates of OS rates for vemurafenib versus Dacarbazine were 56% versus 46%, 30% versus 24%, 21% versus 19% and 17% versus 16% at 1, 2, 3 and 4 years, respectively. Overall, 173 of the 338 patients (51%) in the Dacarbazine arm and 175 of the 337 (52%) of those in the vemurafenib arm received subsequent anticancer therapies, most commonly ipilimumab. Safety data were consistent with the primary analysis. Conclusions: Vemurafenib continues to be associated with improved median OS in the BRIM-3 trial after extended follow-up. OS curves converged after ≈3 years, likely as a result of crossover from Dacarbazine to vemurafenib and receipt of subsequent anticancer therapies. ClinicalTrials.gov: NCT01006980
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nivolumab in previously untreated melanoma without braf mutation
The New England Journal of Medicine, 2015Co-Authors: Caroline Robert, Piotr Rutkowski, C Dutriaux, Jessica C Hassel, Georgina V Long, Benjamin Brady, Michele Maio, L Mortier, Catriona M Mcneil, Ewa KalinkawarzochaAbstract:Nivolumab was associated with higher rates of objective response than chemotherapy in a phase 3 study involving patients with ipilimumab-refractory metastatic melanoma. The use of nivolumab in previously untreated patients with advanced melanoma has not been tested in a phase 3 controlled study. METHODS We randomly assigned 418 previously untreated patients who had metastatic melanoma without a BRAF mutation to receive nivolumab (at a dose of 3 mg per kilogram of body weight every 2 weeks and Dacarbazine-matched placebo every 3 weeks) or Dacarbazine (at a dose of 1000 mg per square meter of body-surface area every 3 weeks and nivolumab-matched placebo every 2 weeks). The primary end point was overall survival. RESULTS At 1 year, the overall rate of survival was 72.9% (95% confidence interval [CI], 65.5 to 78.9) in the nivolumab group, as compared with 42.1% (95% CI, 33.0 to 50.9) in the Dacarbazine group (hazard ratio for death, 0.42; 99.79% CI, 0.25 to 0.73; P<0.001). The median progression-free survival was 5.1 months in the nivolumab group versus 2.2 months in the Dacarbazine group (hazard ratio for death or progression of disease, 0.43; 95% CI, 0.34 to 0.56; P<0.001). The objective response rate was 40.0% (95% CI, 33.3 to 47.0) in the nivolumab group versus 13.9% (95% CI, 9.5 to 19.4) in the Dacarbazine group (odds ratio, 4.06; P<0.001). The survival benefit with nivolumab versus Dacarbazine was observed across prespecified subgroups, including subgroups defined by status regarding the programmed death ligand 1 (PD-L1). Common adverse events associated with nivolumab included fatigue, pruritus, and nausea. Drugrelated adverse events of grade 3 or 4 occurred in 11.7% of the patients treated with nivolumab and 17.6% of those treated with Dacarbazine. CONCLUSIONS Nivolumab was associated with significant improvements in overall survival and progression-free survival, as compared with Dacarbazine, among previously untreated patients who had metastatic melanoma without a BRAF mutation. (Funded by Bristol-Myers Squibb; CheckMate 066 ClinicalTrials.gov number, NCT01721772.)
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Selumetinib plus Dacarbazine versus placebo plus Dacarbazine as first-line treatment for BRAF-mutant metastatic melanoma: a phase 2 double-blind randomised study.
The Lancet. Oncology, 2013Co-Authors: Caroline Robert, Kevin B. Kim, Paul Lorigan, Reinhard Dummer, Ralf Gutzmer, Marta Nyakas, Ana Arance, Gabriella Liszkay, Dirk Schadendorf, Mireille CantariniAbstract:Summary Background Patients with metastatic melanoma, 50% of whose tumours harbour a BRAF mutation, have a poor prognosis. Selumetinib, a MEK1/2 inhibitor, has shown antitumour activity in patients with BRAF -mutant melanoma and in preclinical models when combined with chemotherapy. This study was designed to look for a signal of improved efficacy by comparing the combination of selumetinib and Dacarbazine with Dacarbazine alone. Methods This double-blind, randomised, placebo-controlled phase 2 study investigated selumetinib plus Dacarbazine versus placebo plus Dacarbazine as first-line treatment in patients older than 18 years with histologically or cytologically confirmed advanced BRAF -mutant cutaneous or unknown primary melanoma. Patients were randomly assigned by central interactive voice response system (1:1 ratio, block size four) to take either oral selumetinib (75 mg twice daily in a 21-day cycle) or placebo; all patients received intravenous Dacarbazine (1000 mg/m 2 on day 1 of a 21-day cycle). Patients, investigators, and the study team were masked to the treatment assigned. The primary endpoint was overall survival analysed by intention to treat. This study is registered at ClinicalTrials.gov, NCT00936221. Findings Between July 20, 2009, and April 8, 2010, 91 patients were randomly assigned to receive Dacarbazine in combination with selumetinib (n=45) or placebo (n=46). Overall survival did not differ significantly between groups (median 13·9 months, 80% CI 10·2–15·6, in the selumetinib plus Dacarbazine group and 10·5 months, 9·6–14·7, in the placebo plus Dacarbazine group; hazard ratio [HR] 0·93, 80% CI 0·67–1·28, one-sided p=0·39). However, progression-free survival was significantly improved in the selumetinib plus Dacarbazine group versus the placebo plus Dacarbazine group (HR 0·63, 80% CI 0·47–0·84, one-sided p=0·021), with a median of 5·6 months (80% CI 4·9–5·9) versus 3·0 months (2·8–4·6), respectively. The most frequent adverse events included nausea (28 [64%] of 44 patients on selumetinib vs 25 [56%] of 45 on placebo), acneiform dermatitis (23 [52%] vs one [2%]), diarrhoea (21 [48%] vs 13 [29%]), vomiting (21 [48%] vs 15 [33%]), and peripheral oedema (19 [43%] vs three [7%]). The most common grade 3–4 adverse event was neutropenia (six [14%] patients in the selumetinib plus Dacarbazine group vs four [9%] in the placebo plus Dacarbazine group). Interpretation Selumetinib plus Dacarbazine showed clinical activity in patients with BRAF -mutant cutaneous or unknown primary melanoma, reflected by a significant benefit in progression-free survival compared with placebo plus Dacarbazine group, although no significant change in overall survival was noted. The tolerability of this combination was generally consistent with monotherapy safety profiles. Funding AstraZeneca.
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Pharmacokinetic results of a phase I trial of sorafenib in combination with Dacarbazine in patients with advanced solid tumors
Cancer Chemotherapy and Pharmacology, 2011Co-Authors: Erich Brendel, Caroline Robert, Matthias Ludwig, Chetan Lathia, Stanislas Ropert, Jean-charles Soria, Jean-pierre ArmandAbstract:Purpose Sorafenib, a multikinase inhibitor of Raf and several growth factor receptors, is under investigation in combination with Dacarbazine, a commonly used chemotherapeutic agent for the treatment of many cancers. The current phase I study investigates the effects of sorafenib on the pharmacokinetic (PK) profile of Dacarbazine and its metabolite 5-amino-imidazole-4-carboxamide (AIC). (AIC is formed in amounts equimolar to the active alkylating moiety, methane diazohydroxide, which is undetectable by known validated assays.) Methods Patients with advanced solid tumors received intravenous Dacarbazine 1,000 mg/m^2 on day 1 of a 21-day cycle to evaluate the PK of Dacarbazine alone. Sorafenib 400 mg was administered twice daily continuously starting at day 2 of cycle 1. The PK of Dacarbazine in the presence of sorafenib was assessed on day 1 of cycle 2. Sorafenib PK was also assessed at steady state. Results PK data were available for 15 of 23 patients. With concomitant administration of sorafenib, the mean AUC and C _max values of Dacarbazine were reduced by 23 and 16%, respectively. Mean AUC and C _max values of AIC were increased by 41 and 45%, respectively, with individual increases of up to 106 and 136%, respectively. The apparent terminal half-lives of the two compounds were not significantly influenced by sorafenib. Based on coefficients of variation, the AUC and C _max values for sorafenib and its three metabolites were highly variable with Dacarbazine coadministration. Conclusions Concomitant administration of sorafenib and Dacarbazine as described above may result in decreased Dacarbazine exposure but increased AIC exposure.
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extended schedule escalated dose temozolomide versus Dacarbazine in stage iv melanoma final results of a randomised phase iii study eortc 18032
European Journal of Cancer, 2011Co-Authors: Poulam M. Patel, Cornelis J. A. Punt, Stefan Suciu, Wim H. J. Kruit, Caroline Robert, Reinhard Dummer, Dirk Schadendorf, Laurent Mortier, Uwe Trefzer, Neville DavidsonAbstract:Abstract Purpose To compare the efficacy of an extended schedule escalated dose of temozolomide versus standard dose Dacarbazine in a large population of patients with stage IV melanoma. Patients and methods A total of 859 patients were randomised to receive oral temozolomide at 150 mg/m2/day for seven consecutive days every 2 weeks or Dacarbazine, administered as an intravenous infusion at 1000 mg/m2/day on day 1 every 3 weeks. The primary endpoint was overall survival (OS), using an intent-to-treat principle. EudraCT number 2004-000654-23 NCI registration number NCT00005052. Results Median OS was 9.1 months in the temozolomide arm and 9.4 months in the Dacarbazine arm, with a hazard ratio (HR) of 1.00 (95%confidence interval [CI]: 0.86, 1.17; P = 0.99). Median progression-free survival (PFS) was 2.3 months in the temozolomide arm and 2.2 months in the Dacarbazine arm, with a HR of 0.92 (95%CI: 0.80, 1.06; P = 0.27). In patients with measurable disease, overall response rate was higher in the temozolomide arm than in the Dacarbazine arm (14.5% versus 9.8%, respectively), but the median duration of response was longer for Dacarbazine. The extended schedule, escalated dose temozolomide arm showed more toxicity than the standard dose, single agent Dacarbazine arm. The most common non-haematological treatment emergent adverse events reported in both treatment arms were nausea, fatigue and vomiting and constipation. Conclusion Extended schedule escalated dose Temozolomide (7 days on 7 days off) is feasible and has an acceptable safety profile, but does not improve OS and PFS in metastatic melanoma when compared to standard dose Dacarbazine.
Ascierto, Paolo A. - One of the best experts on this subject based on the ideXlab platform.
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Survival Outcomes in Patients With Previously Untreated BRAF Wild-Type Advanced Melanoma Treated With Nivolumab Therapy Three-Year Follow-up of a Randomized Phase 3 Trial
'American Medical Association (AMA)', 2019Co-Authors: Ascierto, Paolo A., Long Georgina, Robert Caroline, Brady Benjamin, Dutriaux Caroline, Di Giacomo, Anna Maria, Mortier Laurent, Hassel, Jessica C., Rutkowski Piotr, Mcneil CatrionaAbstract:IMPORTANCE This analysis provides long-term follow-up in patients with BRAF wild-type advanced melanoma receiving first-line therapy based on anti-programmed cell death 1 receptor inhibitors. OBJECTIVE To compare the 3-year survival with nivolumab vs that with Dacarbazine in patients with previously untreated BRAF wild-type advanced melanoma. DESIGN, SETTING, AND PARTICIPANTS This follow-up of a randomized phase 3 trial analyzed 3-year overall survival data from the randomized, controlled, double-blind CheckMate 066 phase 3 clinical trial. For this ongoing, multicenter academic institution trial, patients were enrolled from January 2013 through February 2014. Eligible patients were 18 years or older with confirmed unresectable previously untreated stage III or IV melanoma and an Eastern Cooperative Oncology Group performance status of 0 or 1 but without a BRAF mutation. INTERVENTIONS Patients were treated until progression or unacceptable toxic events with nivolumab (3 mg/kg every 2 weeks plus Dacarbazine-matched placebo every 3 weeks) or Dacarbazine (1000 mg/m(2) every 3 weeks plus nivolumab-matched placebo every 2 weeks). MAIN OUTCOME AND MEASURE Overall survival. RESULTS At minimum follow-ups of 38.4 months among 210 participants in the nivolumab group (median age, 64 years [range, 18-86 years]; 57.6% male) and 38.5 months among 208 participants in the Dacarbazine group (median age, 66 years [range, 25-87 years]; 60.1% male), 3-year overall survival rates were 51.2% (95% CI, 44.1%-57.9%) and 21.6% (95% CI, 16.1%-27.6%), respectively. The median overall survival was 37.5 months (95% CI, 25.5 months-not reached) in the nivolumab group and 11.2 months (95% CI, 9.6-13.0 months) in the Dacarbazine group (hazard ratio, 0.46; 95% CI, 0.36-0.59; P < .001). Complete and partial responses, respectively, were reported for 19.0% (40 of 210) and 23.8% (50 of 210) of patients in the nivolumab group compared with 1.4% (3 of 208) and 13.0% (27 of 208) of patients in the Dacarbazine group. Additional analyses were performed on outcomes with subsequent therapies. Treatment-related grade 3/4 adverse events occurred in 15.0% (31 of 206) of nivolumab-treated patients and in 17.6% (36 of 205) of Dacarbazine-treated patients. There were no deaths due to study drug toxic effects. CONCLUSIONS AND RELEVANCE Nivolumab led to improved 3-year overall survival vs Dacarbazine in patients with previously untreated BRAF wild-type advanced melanoma
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Survival outcomes in patients with previously untreated BRAF wild-type advanced melanoma treated with nivolumab therapy. three-year follow-up of a randomized phase 3 trial
'American Medical Association (AMA)', 2019Co-Authors: Ascierto, Paolo A., Hassel, Jessica C., Long G., Robert C., Brady B., Dutriaux C., Di Giacomo A. M., Mortier L., Rutkowski P., Mcneil C.Abstract:Importance: This analysis provides long-term follow-up in patients with BRAF wild-type advanced melanoma receiving first-line therapy based on anti-programmed cell death 1 receptor inhibitors. Objective: To compare the 3-year survival with nivolumab vs that with Dacarbazine in patients with previously untreated BRAF wild-type advanced melanoma. Design, Setting, and Participants: This follow-up of a randomized phase 3 trial analyzed 3-year overall survival data from the randomized, controlled, double-blind CheckMate 066 phase 3 clinical trial. For this ongoing, multicenter academic institution trial, patients were enrolled from January 2013 through February 2014. Eligible patients were 18 years or older with confirmed unresectable previously untreated stage III or IV melanoma and an Eastern Cooperative Oncology Group performance status of 0 or 1 but without a BRAF mutation. Interventions: Patients were treated until progression or unacceptable toxic events with nivolumab (3 mg/kg every 2 weeks plus Dacarbazine-matched placebo every 3 weeks) or Dacarbazine (1000 mg/m 2 every 3 weeks plus nivolumab-matched placebo every 2 weeks). Main Outcome and Measure: Overall survival. Results: At minimum follow-ups of 38.4 months among 210 participants in the nivolumab group (median age, 64 years [range, 18-86 years]; 57.6% male) and 38.5 months among 208 participants in the Dacarbazine group (median age, 66 years [range, 25-87 years]; 60.1% male), 3-year overall survival rates were 51.2% (95% CI, 44.1%-57.9%) and 21.6% (95% CI, 16.1%-27.6%), respectively. The median overall survival was 37.5 months (95% CI, 25.5 months-not reached) in the nivolumab group and 11.2 months (95% CI, 9.6-13.0 months) in the Dacarbazine group (hazard ratio, 0.46; 95% CI, 0.36-0.59; P <.001). Complete and partial responses, respectively, were reported for 19.0% (40 of 210) and 23.8% (50 of 210) of patients in the nivolumab group compared with 1.4% (3 of 208) and 13.0% (27 of 208) of patients in the Dacarbazine group. Additional analyses were performed on outcomes with subsequent therapies. Treatment-related grade 3/4 adverse events occurred in 15.0% (31 of 206) of nivolumab-treated patients and in 17.6% (36 of 205) of Dacarbazine-treated patients. There were no deaths due to study drug toxic effects. Conclusions and Relevance: Nivolumab led to improved 3-year overall survival vs Dacarbazine in patients with previously untreated BRAF wild-type advanced melanoma. Trial Registration: ClinicalTrials.gov identifier: NCT01721772
Mcneil Catriona - One of the best experts on this subject based on the ideXlab platform.
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Survival Outcomes in Patients With Previously Untreated BRAF Wild-Type Advanced Melanoma Treated With Nivolumab Therapy Three-Year Follow-up of a Randomized Phase 3 Trial
'American Medical Association (AMA)', 2019Co-Authors: Ascierto, Paolo A., Long Georgina, Robert Caroline, Brady Benjamin, Dutriaux Caroline, Di Giacomo, Anna Maria, Mortier Laurent, Hassel, Jessica C., Rutkowski Piotr, Mcneil CatrionaAbstract:IMPORTANCE This analysis provides long-term follow-up in patients with BRAF wild-type advanced melanoma receiving first-line therapy based on anti-programmed cell death 1 receptor inhibitors. OBJECTIVE To compare the 3-year survival with nivolumab vs that with Dacarbazine in patients with previously untreated BRAF wild-type advanced melanoma. DESIGN, SETTING, AND PARTICIPANTS This follow-up of a randomized phase 3 trial analyzed 3-year overall survival data from the randomized, controlled, double-blind CheckMate 066 phase 3 clinical trial. For this ongoing, multicenter academic institution trial, patients were enrolled from January 2013 through February 2014. Eligible patients were 18 years or older with confirmed unresectable previously untreated stage III or IV melanoma and an Eastern Cooperative Oncology Group performance status of 0 or 1 but without a BRAF mutation. INTERVENTIONS Patients were treated until progression or unacceptable toxic events with nivolumab (3 mg/kg every 2 weeks plus Dacarbazine-matched placebo every 3 weeks) or Dacarbazine (1000 mg/m(2) every 3 weeks plus nivolumab-matched placebo every 2 weeks). MAIN OUTCOME AND MEASURE Overall survival. RESULTS At minimum follow-ups of 38.4 months among 210 participants in the nivolumab group (median age, 64 years [range, 18-86 years]; 57.6% male) and 38.5 months among 208 participants in the Dacarbazine group (median age, 66 years [range, 25-87 years]; 60.1% male), 3-year overall survival rates were 51.2% (95% CI, 44.1%-57.9%) and 21.6% (95% CI, 16.1%-27.6%), respectively. The median overall survival was 37.5 months (95% CI, 25.5 months-not reached) in the nivolumab group and 11.2 months (95% CI, 9.6-13.0 months) in the Dacarbazine group (hazard ratio, 0.46; 95% CI, 0.36-0.59; P < .001). Complete and partial responses, respectively, were reported for 19.0% (40 of 210) and 23.8% (50 of 210) of patients in the nivolumab group compared with 1.4% (3 of 208) and 13.0% (27 of 208) of patients in the Dacarbazine group. Additional analyses were performed on outcomes with subsequent therapies. Treatment-related grade 3/4 adverse events occurred in 15.0% (31 of 206) of nivolumab-treated patients and in 17.6% (36 of 205) of Dacarbazine-treated patients. There were no deaths due to study drug toxic effects. CONCLUSIONS AND RELEVANCE Nivolumab led to improved 3-year overall survival vs Dacarbazine in patients with previously untreated BRAF wild-type advanced melanoma
Mcneil C. - One of the best experts on this subject based on the ideXlab platform.
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Survival outcomes in patients with previously untreated BRAF wild-type advanced melanoma treated with nivolumab therapy. three-year follow-up of a randomized phase 3 trial
'American Medical Association (AMA)', 2019Co-Authors: Ascierto, Paolo A., Hassel, Jessica C., Long G., Robert C., Brady B., Dutriaux C., Di Giacomo A. M., Mortier L., Rutkowski P., Mcneil C.Abstract:Importance: This analysis provides long-term follow-up in patients with BRAF wild-type advanced melanoma receiving first-line therapy based on anti-programmed cell death 1 receptor inhibitors. Objective: To compare the 3-year survival with nivolumab vs that with Dacarbazine in patients with previously untreated BRAF wild-type advanced melanoma. Design, Setting, and Participants: This follow-up of a randomized phase 3 trial analyzed 3-year overall survival data from the randomized, controlled, double-blind CheckMate 066 phase 3 clinical trial. For this ongoing, multicenter academic institution trial, patients were enrolled from January 2013 through February 2014. Eligible patients were 18 years or older with confirmed unresectable previously untreated stage III or IV melanoma and an Eastern Cooperative Oncology Group performance status of 0 or 1 but without a BRAF mutation. Interventions: Patients were treated until progression or unacceptable toxic events with nivolumab (3 mg/kg every 2 weeks plus Dacarbazine-matched placebo every 3 weeks) or Dacarbazine (1000 mg/m 2 every 3 weeks plus nivolumab-matched placebo every 2 weeks). Main Outcome and Measure: Overall survival. Results: At minimum follow-ups of 38.4 months among 210 participants in the nivolumab group (median age, 64 years [range, 18-86 years]; 57.6% male) and 38.5 months among 208 participants in the Dacarbazine group (median age, 66 years [range, 25-87 years]; 60.1% male), 3-year overall survival rates were 51.2% (95% CI, 44.1%-57.9%) and 21.6% (95% CI, 16.1%-27.6%), respectively. The median overall survival was 37.5 months (95% CI, 25.5 months-not reached) in the nivolumab group and 11.2 months (95% CI, 9.6-13.0 months) in the Dacarbazine group (hazard ratio, 0.46; 95% CI, 0.36-0.59; P <.001). Complete and partial responses, respectively, were reported for 19.0% (40 of 210) and 23.8% (50 of 210) of patients in the nivolumab group compared with 1.4% (3 of 208) and 13.0% (27 of 208) of patients in the Dacarbazine group. Additional analyses were performed on outcomes with subsequent therapies. Treatment-related grade 3/4 adverse events occurred in 15.0% (31 of 206) of nivolumab-treated patients and in 17.6% (36 of 205) of Dacarbazine-treated patients. There were no deaths due to study drug toxic effects. Conclusions and Relevance: Nivolumab led to improved 3-year overall survival vs Dacarbazine in patients with previously untreated BRAF wild-type advanced melanoma. Trial Registration: ClinicalTrials.gov identifier: NCT01721772
Hassel, Jessica C. - One of the best experts on this subject based on the ideXlab platform.
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Survival Outcomes in Patients With Previously Untreated BRAF Wild-Type Advanced Melanoma Treated With Nivolumab Therapy Three-Year Follow-up of a Randomized Phase 3 Trial
'American Medical Association (AMA)', 2019Co-Authors: Ascierto, Paolo A., Long Georgina, Robert Caroline, Brady Benjamin, Dutriaux Caroline, Di Giacomo, Anna Maria, Mortier Laurent, Hassel, Jessica C., Rutkowski Piotr, Mcneil CatrionaAbstract:IMPORTANCE This analysis provides long-term follow-up in patients with BRAF wild-type advanced melanoma receiving first-line therapy based on anti-programmed cell death 1 receptor inhibitors. OBJECTIVE To compare the 3-year survival with nivolumab vs that with Dacarbazine in patients with previously untreated BRAF wild-type advanced melanoma. DESIGN, SETTING, AND PARTICIPANTS This follow-up of a randomized phase 3 trial analyzed 3-year overall survival data from the randomized, controlled, double-blind CheckMate 066 phase 3 clinical trial. For this ongoing, multicenter academic institution trial, patients were enrolled from January 2013 through February 2014. Eligible patients were 18 years or older with confirmed unresectable previously untreated stage III or IV melanoma and an Eastern Cooperative Oncology Group performance status of 0 or 1 but without a BRAF mutation. INTERVENTIONS Patients were treated until progression or unacceptable toxic events with nivolumab (3 mg/kg every 2 weeks plus Dacarbazine-matched placebo every 3 weeks) or Dacarbazine (1000 mg/m(2) every 3 weeks plus nivolumab-matched placebo every 2 weeks). MAIN OUTCOME AND MEASURE Overall survival. RESULTS At minimum follow-ups of 38.4 months among 210 participants in the nivolumab group (median age, 64 years [range, 18-86 years]; 57.6% male) and 38.5 months among 208 participants in the Dacarbazine group (median age, 66 years [range, 25-87 years]; 60.1% male), 3-year overall survival rates were 51.2% (95% CI, 44.1%-57.9%) and 21.6% (95% CI, 16.1%-27.6%), respectively. The median overall survival was 37.5 months (95% CI, 25.5 months-not reached) in the nivolumab group and 11.2 months (95% CI, 9.6-13.0 months) in the Dacarbazine group (hazard ratio, 0.46; 95% CI, 0.36-0.59; P < .001). Complete and partial responses, respectively, were reported for 19.0% (40 of 210) and 23.8% (50 of 210) of patients in the nivolumab group compared with 1.4% (3 of 208) and 13.0% (27 of 208) of patients in the Dacarbazine group. Additional analyses were performed on outcomes with subsequent therapies. Treatment-related grade 3/4 adverse events occurred in 15.0% (31 of 206) of nivolumab-treated patients and in 17.6% (36 of 205) of Dacarbazine-treated patients. There were no deaths due to study drug toxic effects. CONCLUSIONS AND RELEVANCE Nivolumab led to improved 3-year overall survival vs Dacarbazine in patients with previously untreated BRAF wild-type advanced melanoma
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Survival outcomes in patients with previously untreated BRAF wild-type advanced melanoma treated with nivolumab therapy. three-year follow-up of a randomized phase 3 trial
'American Medical Association (AMA)', 2019Co-Authors: Ascierto, Paolo A., Hassel, Jessica C., Long G., Robert C., Brady B., Dutriaux C., Di Giacomo A. M., Mortier L., Rutkowski P., Mcneil C.Abstract:Importance: This analysis provides long-term follow-up in patients with BRAF wild-type advanced melanoma receiving first-line therapy based on anti-programmed cell death 1 receptor inhibitors. Objective: To compare the 3-year survival with nivolumab vs that with Dacarbazine in patients with previously untreated BRAF wild-type advanced melanoma. Design, Setting, and Participants: This follow-up of a randomized phase 3 trial analyzed 3-year overall survival data from the randomized, controlled, double-blind CheckMate 066 phase 3 clinical trial. For this ongoing, multicenter academic institution trial, patients were enrolled from January 2013 through February 2014. Eligible patients were 18 years or older with confirmed unresectable previously untreated stage III or IV melanoma and an Eastern Cooperative Oncology Group performance status of 0 or 1 but without a BRAF mutation. Interventions: Patients were treated until progression or unacceptable toxic events with nivolumab (3 mg/kg every 2 weeks plus Dacarbazine-matched placebo every 3 weeks) or Dacarbazine (1000 mg/m 2 every 3 weeks plus nivolumab-matched placebo every 2 weeks). Main Outcome and Measure: Overall survival. Results: At minimum follow-ups of 38.4 months among 210 participants in the nivolumab group (median age, 64 years [range, 18-86 years]; 57.6% male) and 38.5 months among 208 participants in the Dacarbazine group (median age, 66 years [range, 25-87 years]; 60.1% male), 3-year overall survival rates were 51.2% (95% CI, 44.1%-57.9%) and 21.6% (95% CI, 16.1%-27.6%), respectively. The median overall survival was 37.5 months (95% CI, 25.5 months-not reached) in the nivolumab group and 11.2 months (95% CI, 9.6-13.0 months) in the Dacarbazine group (hazard ratio, 0.46; 95% CI, 0.36-0.59; P <.001). Complete and partial responses, respectively, were reported for 19.0% (40 of 210) and 23.8% (50 of 210) of patients in the nivolumab group compared with 1.4% (3 of 208) and 13.0% (27 of 208) of patients in the Dacarbazine group. Additional analyses were performed on outcomes with subsequent therapies. Treatment-related grade 3/4 adverse events occurred in 15.0% (31 of 206) of nivolumab-treated patients and in 17.6% (36 of 205) of Dacarbazine-treated patients. There were no deaths due to study drug toxic effects. Conclusions and Relevance: Nivolumab led to improved 3-year overall survival vs Dacarbazine in patients with previously untreated BRAF wild-type advanced melanoma. Trial Registration: ClinicalTrials.gov identifier: NCT01721772
