Lung Cancer, Melanoma Drug Approval Highlight Oncology News

Elotuzumab Approved for Multiple Myeloma

The FDA approved elotuzumab for use in combination with lenalidomide and dexamethasone for patients with multiple myeloma following the failure of 1 to 3 prior therapies. The approval was based on data from the phase III ELOQUENT-2 trial, in which the 3-drug elotuzumab combination reduced the risk of disease progression by 30% compared with lenalidomide/dexamethasone alone.

At a median follow-up of 2 years, PFS with the elotuzumab regimen was 19.4 months versus 14.9 months with lenalidomide and dexamethasone alone (HR, 0.70; P <.001). The 1-year PFS for the elotuzumab versus control arm was 68% versus 57%, respectively, with the difference in 2-year PFS rates increasing to 41% versus 27%. The PFS benefit with elotuzumab in the overall study was observed across the high-risk del(17p) and t(4;14) subgroups, with HRs of 0.65 and 0.53, respectively. ORR was 79% with elotuzumab and 66% for the control group (P <.001).

The OS data for the trial are not yet mature. This decision marks the third approval for multiple myeloma in November. Earlier in the month, the FDA also approved the oral proteasome inhibitor ixazomib and the CD38 antibody daratumumab.

See more at: http://www.onclive.com/web-exclusives/fda-approves-elotuzumab-for-multiple-myeloma

Necitumumab Approved for Squamous NSCLC

The FDA approved necitumumab in combination with gemcitabine and cisplatin for the first-line treatment of patients with locally advanced or metastatic squamous non—small cell lung cancer, based findings from the phase III SQUIRE trial. In the 1093-patient study, the addition of the fully human IgG1 anti-EGFR monoclonal antibody necitumumab to gemcitabine and cisplatin improved overall survival by 1.6 months, which was equivalent to a 16% reduction in the risk of death.

Progression-free survival was improved by 15% with the triplet therapy. After a follow-up of approximately 25 months, the median OS was 11.5 months in the necitumumab arm versus 9.9 months with the chemotherapy alone (HR, 0.84; P = .012).

The median PFS with necitumumab was 5.7 versus 5.5 months for chemotherapy alone (HR, 0.85; P = .02). The ORR was 31% in the necitumumab arm and 29% with the chemotherapy alone (P = .40). The FDA approval follows an informal recommendation from the Oncologic Drugs Advisory Committee in July 2015. Following a discussion on the clinical trial results from the SQUIRE trial, the consensus of the panel was that the benefits of necitumumab were modest, yet clinically significant.

See more at: http://www.onclive.com/web-exclusives/fda-approves-necitumumab-for-squamous-nsclc

Frontline Nivolumab Approved for BRAF Wild-Type Melanoma

The FDA expanded the approval for single-agent nivolumab to include the frontline treatment of patients with BRAF wild-type advanced melanoma, based on a substantial improvement in overall survival compared with dacarbazine in a phase III study. In data from the CheckMate-066 trial assessed by the FDA, median OS with nivolumab was not reached versus 10.8 months for dacarbazine, representing a 58% reduction in the risk of death (HR, 0.42; P <.0001).

Median progression-free survival with nivolumab was 5.1 versus 2.2 months for dacarbazine (HR, 0.43; P <.0001). In updated data presented at the 2015 Society for Melanoma Research Congress, the 2-year OS rate with frontline nivolumab was 57.7% compared with 26.7% for dacarbazine. The application that was the basis for this approval was emended in August to be for patients regardless of BRAF status.

However, for the BRAF mutant population, the FDA issued a complete response letter requesting additional data. A separate application was also submitted for BRAF-mutant advanced melanoma, based on phase III data from the CheckMate-067 trial. This application was granted a priority review, with a decision deadline of January 23, 2016. In this study, those with BRAF-mutations treated with single-agent nivolumab (n = 98) had a median PFS of 5.6 months compared with 4.0 months with single-agent ipilimumab (n = 100; HR, 0.77).

See more on the complete response letter at: http://www.onclive.com/web-exclusives/fda-issues-complete-response-letter-for-nivolumab-in-braf-mutant-melanoma

Vemurafenib/Cobimetinib Combo Approved in Europe

On Wednesday, the European Commission approved the combination of vemurafenib and cobimetinib as a treatment for patients with BRAF-positive metastatic or unresectable melanoma, based on the phase III coBRIM study. In the data submitted to the EC, the median progression-free survival with the combination was 12.3 months versus 7.2 months for vemurafenib alone (HR, 0.58; P <.001).

At a 17-month analysis, 65% of patients receiving the combination remained alive versus 50% for vemurafenib. The objective response rate with the combination was 70% compared with 50% for vemurafenib alone. OS data from coBRIM were recently presented at the 2015 Society for Melanoma Research Congress. The median OS was 22.3 months with vemurafenib/cobimetinib versus 17.4 months with vemurafenib alone, representing a 30% reduction in the risk of death (HR, 0.70; P = .005).

The 1- and 2-year OS rates with the combination were 74.5% and 48.3%, respectively. The FDA approved the combination in the United States on November 10, 2015.

See more on the European approval at: http://www.onclive.com/web-exclusives/european-commission-approves-vemurafenibcobimetinib-combo-for-melanoma

Here’s what’s currently in the FDA regulatory pipeline for the next 4 months:

• Pembrolizumab Frontline Melanoma - December 19, 2015
• Pembrolizumab Ipilimumab-Refractory Melanoma - December 24, 2015
• Maintenance ofatumumab CLL - January 21, 2016
• Carfilzomib Relapsed Myeloma - January 22, 2016
• Frontline nivolumab BRAF-mutant melanoma - Januaruy 23, 2016
• MCNA Bladder Cancer - February 27, 2016 (Uncertain)
• Alectinib ALK+ NSCLC - March 4, 2016
• Eribulin in STS - March 30, 2016