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Extended Survival from Melanoma Drug Highlights Week in Cancer News
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Top news of the week in cancer research.
Encorafenib/Binimetinib Improves PFS in COLUMBUS Trial
The combination of the BRAF inhibitor encorafenib and the MEK inhibitor binimetinib improved progression-free survival by 7.6 months compared with single-agent vemurafenib for patients with BRAF-mutant melanoma, according to findings from part 1 of the phase III COLUMBUS trial. Array said the combination was “well tolerated,” although it did not release exact details on the adverse event profile.
Median PFS was 14.9 months with the combination of encorafenib and binimetinib compared with 7.3 months for vemurafenib alone, according to the developer of the combination, Array BioPharma. The improvement in PFS represented a 46% reduction in the risk of progression or death (HR, 0.54; P <.001). Single-agent encorafenib showed a median PFS of 9.6 versus 14.9 months with the combination, which did not reach statistical significance at the time of the analysis (HR, 0.75; P = .051).
A full analysis of part 2 of the study will further illuminate findings for the comparison of the combination and encorafenib monotherapy. Array plans to submit data from the study to the FDA and EMA in 2017.
Approval Sought for Ibrutinib in MZL
A supplemental new drug application has been submitted to the FDA for the use of ibrutinib as a treatment for patients with marginal zone lymphoma. The sNDA is based on the phase II PCYC-1121 trial, which examined single-agent ibrutinib in patients with MZL following at least 1 prior therapy. Results from the trial will be presented at an upcoming medical meeting.
The single-arm, open-label, international PCYC-1121 trial included 63 patients with splenic MZL, nodal MZL, or extranodal MZL. Patients were required to have received 1 or more prior therapies, including at least 1 anti-CD20 regimen. A prior phase I study had shown cursory efficacy for ibrutinib in patients with MZL. In this study, among the 4 patients with MZL, 1 had a PR, 1 had stable disease, 1 had progressive disease, and 1 was not evaluable.
See more: http://www.onclive.com/web-exclusives/fda-approval-sought-for-ibrutinib-in-marginal-zone-lymphoma
Frontline Ceritinib Bests Chemo for ALK+ NSCLC
Ceritinib improved progression-free survival compared with standard chemotherapy as a first-line treatment for patients with ALK-positive non—small cell lung cancer, according to results from the phase III ASCEND-4 trial.
Beyond reaching the study’s primary PFS endpoint, ceritinib also met key secondary outcome measures, including objective response rate and duration of response. The safety profile was consistent with previous adverse event data reported for ceritinib. Prior findings from the phase II ASCEND-3 study showed an ORR of 63.7% with ceritinib, including 29 of 50 (58%) patients with brain metastases and 50 of 74 (67.6%) patients without brain metastases.
Median duration of response was 9.3 months and the median PFS was 11.1 months. The median PFS was 10.8 and 11.1 months in patients with and without brain metastases, respectively. Novartis plans to present the ASCEND-4 data from at an upcoming medical meeting and will submit the findings to various regulatory agencies in the next few months.
See more: http://www.onclive.com/web-exclusives/frontline-ceritinib-delays-progression-in-alk-nsclc
FDA Accepts NDA for Neratinib in Breast Cancer
The FDA has accepted a new drug application for neratinib as an extended adjuvant therapy for patients with HER2-positive breast cancer following prior treatment with postoperative trastuzumab. The application included findings from the phase III ExteNET study.
The FDA completes a standard review within 12 months from the time of submission, which was completed for neratinib on July 21, 2016. The application was originally anticipated in the first quarter of 2016; however, the submission was delayed following a series of meetings with the FDA in which the agency requested a new statistical analysis of data from the ExteNET trial. For the new analysis, data were censored for patients who missed 2 or more scheduled disease assessments prior to recurrence or death.
With the new statistical model, the 2-year invasive DFS rates were 94.2% and 91.9% for neratinib and placebo, respectively. This represented a 34% reduction in the risk of disease recurrence or death (HR, 0.66; P = .004). The NDA was based on the new statistical analysis of the ExteNET data, which has not yet been published. Additionally, further data were submitted from a phase II study exploring diarrhea prophylaxis with loperamide.
See more: http://www.onclive.com/web-exclusives/fda-accepts-neratinib-nda-for-her2positive-breast-cancer
EMA Accepts Nivolumab Application for Bladder Cancer
The European Medicines Agency has validated a type II variation application for use of nivolumab as a treatment for patients with locally advanced unresectable or metastatic urothelial carcinoma who have progressed following platinum-based chemotherapy. The validation confirms the completion of the submission process and starts the formal review by the Committee for Medicinal Products for Human Use and the subsequent final approval decision by the European Commission.
The application was based on findings from the open-label, single-arm CheckMate-275 study, which is examining nivolumab in previously treated patients with mUC. Objective response rate is the primary endpoint of the trial, with secondary outcome measures including overall survival and durability of response. Findings from the trial will be presented at the 2016 ESMO Annual Congress in October.
In the prior CheckMate-032 trial single-agent nivolumab had an ORR of nearly 25% in patients with advanced mUC. The median progression-free survival was 2.78 months (95% CI, 1.45-5.85) and the median OS was 9.72 months (95% CI, 7.26-16.16).
See more: http://www.onclive.com/web-exclusives/ema-initiates-official-review-of-nivolumab-in-bladder-cancer
