Melanoma Approvals Highlight Oncology News Review

FDA Expands Pembrolizumab Melanoma Approval

The FDA has expanded the approval for single-agent pembrolizumab to include the frontline treatment of patients with advanced melanoma regardless of BRAF status and as a treatment for patients with ipilimumab-refractory melanoma. The frontline decision was based on a substantial improvement in progression-free and overall survival compared with ipilimumab in the phase III KEYNOTE-006 trial.

At a 6-month assessment, the progression-free survival rate with pembrolizumab was 47.3% and 46.4% in the 2- and 3-week arms respectively, compared with 26.5% for the ipilimumab arm (HR, 0.58; P <.001). The 1-year overall survival rate was 74.1% for the 2-week pembrolizumab arm versus 58.2% for those receiving ipilimumab (HR, 0.63; P <.0005). In the 3-week pembrolizumab group, the 1-year OS rate was 68.4% (HR vs ipilimumab, 0.69; P = .0036).

The second indication was based on the KEYNOTE-002 study. In this study, the risk of disease progression or death was reduced by 43% with pembrolizumab at 2 mg/kg compared with chemotherapy (HR, 0.57; P <.0001). At the 2-mg/kg dose, the ORR with pembrolizumab was 21% with a median DOR not yet reached.

See more at: http://www.onclive.com/web-exclusives/fda-approves-two-new-indications-for-pembrolizumab-in-advanced-melanoma

T-VEC Approved for Melanoma in Europe

The European Commission has approved T-VEC as a treatment for adult patients with unresectable stage IIIb, IIIc, and IVM1a melanoma that has not spread to the bone, brain, lung, or other viscera, based on the phase III OPTiM study.

In the study, T-VEC significantly extended durable response rates compared with GM-CSF. The DRR with T-VEC in those with stage IIIb, IIIc, and IVM1a melanoma was 25.2% versus 1.2% with GM-CSF. In these same groups, median overall survival was 41.1 months with T-VEC compared with 21.5 months with GM-CSF; however, the study was not designed to look specifically at these groups.

In the subgroup analysis, differences in DRR were more pronounced in patients with stage IIIb/c melanoma (33% vs 0%). In the stage IVM1a group, the DRR was 16% with T-VEC versus 2% with GM-CSF. The differences were less pronounced in the more advanced groups (IVM1b, 3% vs 4%; IVM1c, 7% vs 3%).

Across the full study, the DRR was 16.3% with T-VEC compared with 2.1% for GM-CSF. The objective response rate was 26.4% versus 5.7% and the complete response rate was 11% compared with 1%, for T-VEC and GM-CSF, respectively.

See more at: http://www.onclive.com/web-exclusives/t-vec-approved-in-europe-for-unresectable-metastatic-melanoma

Binimetinib Improves PFS in NRAS-Mutant Melanoma

The MEK inhibitor binimetinib has shown an improvement in progression-free survival compared with dacarbazine in patients with advanced NRAS-mutant melanoma, according to top-line findings from a phase III released by Array BioPharma. In the open-label trial, labeled NEMO, binimetinib reduced the risk of progression or death by 38% versus dacarbazine (HR, 0.62; P <.0001).

Median PFS with binimetinib was 2.8 versus 1.5 months with dacarbazine. The primary endpoint of the study was PFS by blinded independent review. Secondary outcome measures focused on overall survival, response, and safety. Full findings from the study, including outcomes based on prior immunotherapy, will be presented at a medical meeting in 2016.

Given the responses seen with immunotherapy for NRAS-mutant melanoma, the binimetinib would likely be used as a second-line therapy. Array BioPharma plans to submit data from NEMO to the FDA in the first half of 2016.

See more at: http://www.onclive.com/web-exclusives/binimetinib-improves-pfs-in-nras-mutant-melanoma

Rociletinib Decision Delayed for NSCLC

The FDA has extended the review period for rociletinib in patients with EGFR T790M-positive non—small cell lung cancer by 3 months, to allow ample time to review additional data. The action date for the new drug application is now June 28, 2016.

The delay follows a request for additional data from the FDA, as a result of response rate changes in the two ongoing single-arm trials that were the basis for the new drug application. In the updated results released by Clovis, evaluable patients treated with the 500 mg dose of rociletinib (n = 79) experienced a confirmed objective response rate of 28%.

Additionally, in 170 patients treated with the 625 mg dose, the confirmed ORR was 34%. The duration of response for both doses was 9 months. The extension in the review period was expected.

In the earlier data presented at the 2015 ASCO Annual Meeting, the ORR across all dose levels was 53% and a disease control rate was 85%. Specifically for those who received the 500 mg dose, the ORR was 60% and a disease control rate was 90%.

See more at: http://www.onclive.com/web-exclusives/fda-delays-decision-on-rociletinib-in-nsclc

Pembrolizumab Improves OS in PD-L1-Positive NSCLC

Treatment with pembrolizumab reduced the risk of death by 29% compared with docetaxel for patients with PD-L1-positive non—small cell lung cancer, according to findings from the phase II/III KEYNOTE-010 study. In the open-label study, median overall survival was 10.4 months with the FDA-approved dose of 2 mg/kg of pembrolizumab compared with 8.5 months with docetaxel in those with >1% PD-L1 expression (HR, 0.71; P = .0008).

With a larger dose of pembrolizumab (10 mg/kg), the median OS was 12.7 months, representing a 39% reduction in the risk of death versus docetaxel (HR, 0.61; P <.0001). The FDA granted an accelerated approval to pembrolizumab as a treatment for patients with NSCLC that had ≥50% PD-L1 expression on October 2, 2015.

Findings from the KEYNOTE-010 study will be submitted to the FDA and European Medicines Agency within the coming months to expand this approval, according to the developer of the drug, Merck. Median PFS was not significantly improved with pembrolizumab in those with >1% expression, possibly due to pseudoprogression.

PFS was improved with pembrolizumab in those with ≥50% PD-L1 expression.

See more at: http://www.onclive.com/web-exclusives/pembrolizumab-improves-survival-in-pd-l1-positive-nsclc