Dataset Information

Health-related quality of life impact of cobimetinib in combination with vemurafenib in patients with advanced or metastatic BRAFV600 mutation-positive melanoma.

ABSTRACT: BACKGROUND:In the coBRIM study, cobimetinib plus vemurafenib (C+V) significantly improved survival outcomes vs placebo and vemurafenib (P+V) in patients with advanced/metastatic BRAFV600-mutated melanoma. An analysis of health-related quality of life (HRQOL) from coBRIM is reported. METHODS:Patients completing the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (QLQ-C30) at baseline and ?1 time point thereafter constituted the analysis population. Change from baseline ?10 points was considered clinically meaningful. RESULTS:Mean baseline scores for all QLQ-C30 domains were similar between arms. Most on-treatment scores for QLQ-C30 domains were also comparable between arms. A transient deterioration in role function in cycle 1?day 15 (C1D15; -14.7 points) in the P+V arm and improvement in insomnia in the C+V arm at C2D15 (-12.4 points) was observed. Among patients who experienced a ?10-point change from baseline (responders), between-group differences were greatest for insomnia (16%), social functioning (10%), fatigue (9%) and pain (7%), all favouring C+V. Diarrhoea, photosensitivity reaction, pyrexia, and rash did not meaningfully affect global health status (GHS). Serous retinopathy was associated with a transient decrease in GHS at C1D15 assessment. CONCLUSIONS:In patients with advanced/metastatic BRAFV600-mutated melanoma, treatment with C+V maintained HRQOL compared with P+V, with superior efficacy.

SUBMITTER: Dreno B

PROVIDER: S-EPMC5877437 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Health-related quality of life impact of cobimetinib in combination with vemurafenib in patients with advanced or metastatic BRAF<sup>V600</sup> mutation-positive melanoma.

Dréno Brigitte B Ascierto Paolo A PA Atkinson Victoria V Liszkay Gabriella G Maio Michele M Mandalà Mario M Demidov Lev L Stroyakovskiy Daniil D Thomas Luc L de la Cruz-Merino Luis L Dutriaux Caroline C Garbe Claus C Bartley Karen K Karagiannis Thomas T Chang Ilsung I Rooney Isabelle I Koralek Daniel O DO Larkin James J McArthur Grant A GA Ribas Antoni A

British journal of cancer 20180213 6

<h4>Background</h4>In the coBRIM study, cobimetinib plus vemurafenib (C+V) significantly improved survival outcomes vs placebo and vemurafenib (P+V) in patients with advanced/metastatic BRAF<sup>V600</sup>-mutated melanoma. An analysis of health-related quality of life (HRQOL) from coBRIM is reported.<h4>Methods</h4>Patients completing the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (QLQ-C30) at baseline and ⩾1 time point thereafter constitute ...[more]

PMID: 29438370

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Project description:BackgroundThe 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 methodsPatients 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.ResultsBetween 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.ConclusionsVemurafenib 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.govNCT01006980.

Project description:BackgroundStudies carried out in vitro and in a mouse model have shown that BRAF inhibitors enhance the effects of IFN-α on BRAFV600E melanoma cells through the inhibition of ERK. Therefore, the combination of vemurafenib and IFN-α in patients with BRAFV600E melanoma may provide therapeutic benefits; MEK inhibition may prevent the reactivation of the MAPK pathway induced by BRAF inhibitor resistance.Patients and methodsIn a phase I study, adult patients with advanced BRAFV600-mutated melanoma were treated with vemurafenib + PEG-IFN-α-2b or vemurafenib + cobimetinib + PEG-IFN-α-2b, to assess the safety of the combination and the upregulation of IFN-α/β receptor-1 (IFNAR1).ResultsEight patients were treated; 59 adverse events with four serious ones (three related to study treatments) were reported. Patients with a pre-treatment IFNAR1 expression on ≤ 35% melanoma cells had a median progression-free survival of 12.0 months (range: 5.6-18.4 months) and a median overall survival of 31.0 months (range: 19.8-42.2 months), while patients with a pre-treatment IFNAR1 expression on > 35% of melanoma cells had a median progression-free survival of 4.0 months (range: 0-8.8; p = 0.03), and a median overall survival of 5 months (p = 0.02). Following treatment, responders had higher levels of growth-suppressor genes, including GAS1 and DUSP1, and genes involved in a metabolically robust immune response, including FAP.ConclusionOur study supports the overall safety of the vemurafenib + PEG-IFN-α-2b + cobimetinib combination. IFNAR1 expression levels correlated with response to treatment, including survival. Vemurafenib + PEG-IFN-α-2b + cobimetinib would have difficulty finding a niche in the current treatment scenario for advanced melanoma, but we speculate that our findings may contribute to identify subjects particularly responsive to treatment.Trial registrationThe study was registered at clinicaltrials.gov (NCT01959633). Registered 10 October 2013, https://clinicaltrials.gov/ct2/show/NCT01959633.

Project description:ImportanceIn the IMspire150 trial, triplet treatment with atezolizumab and vemurafenib plus cobimetinib significantly improved progression-free survival (PFS) compared with vemurafenib plus cobimetinib alone for treatment of BRAF V600 variation metastatic melanoma. However, considering high cost of this combination, it is unclear if the incremental cost is worth the additional survival benefit.ObjectiveTo evaluate the cost-effectiveness of atezolizumab and vemurafenib plus cobimetinib vs vemurafenib plus cobimetinib alone in patients with newly diagnosed unresectable BRAF V600 variation metastatic melanoma from the US health care perspective.Design, setting, and participantsThis economic evaluation study used a 3-state partitioned survival model to assess the cost-effectiveness of the combination of atezolizumab with vemurafenib plus cobimetinib vs vemurafenib plus cobimetinib alone. The observed Kaplan-Meier curves for overall survival and PFS were digitized from the IMspire150 trial (January 2017-April 2018) and the long-term survivals (over a lifetime horizon) beyond the end of the trial were extrapolated using 7 different survival models. The cost and health preference data were collected from a literature review. This study was performed from March 2021 through June 2021.Main outcomes and measuresThe outcomes of interest were expected life-years (LYs) gained and quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratio (ICER), expressed as cost per LYs and per QALYs saved.ResultsAdding atezolizumab to vemurafenib and cobimetinib provided an additional 3.267 QALYs compared with the doublet regimen of vemurafenib plus cobimetinib, at an ICER of $271 669 per QALY, which is not considered cost-effective at the willingness-to-pay threshold of $150 000 per QALY. However, the scenario analyses found that atezolizumab combined with vemurafenib plus cobimetinib could be cost-effective at 20-year (ICER, $121 432 per QALY) and 30-year ($98 092 per QALY) time horizons when both strategies were stopped after 2 years of treatments, and over a lifetime horizon ($122 220 per QALY) when only immunotherapy with atezolizumab was stopped after 2 years of treatment.Conclusions and relevanceThese findings suggest that the atezolizumab and vemurafenib plus cobimetinib regimen provides significant survival benefits over vemurafenib plus cobimetinib alone, and a price reduction would be encouraged to maximize the value of its survival gain.

Dataset Information

Health-related quality of life impact of cobimetinib in combination with vemurafenib in patients with advanced or metastatic BRAFV600 mutation-positive melanoma.

Publications

Health-related quality of life impact of cobimetinib in combination with vemurafenib in patients with advanced or metastatic BRAF<sup>V600</sup> mutation-positive melanoma.

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