FDA approves treatments for advanced melanoma, lung cancer

October 2, 2015

FDA has approved cancer therapies, one targeting metastatic melanoma and the other for metastatic non-small cell lung cancer (NSCLC).

FDA has approved cancer therapies, one targeting metastatic melanoma and the other for metastatic non-small cell lung cancer (NSCLC).

Staff Picks: New drugs raise hopes

Metastatic melanoma therapy

Bristol-Myers Squibb received FDA approval for its two-drug therapy regimen of immune-oncology agents, nivolumab (Opdivo) and ipilimumab (Yervoy), for the treatment of patients with BRAF V600 wild-type unresectable or metastatic melanoma. Ipilimumab was approved four years ago for metastatic melanoma and nivolumab was approved late last year.

The combination drug regimen approval was based on results from the CheckMate-069 study, a phase 2 trial of 140 patients with previously untreated advanced melanoma. Patients had BRAF wide-type or BRAF mutation-positive melanoma. Patients were randomized to receive the Regimen of four cycles of the combination treatment followed by nivolumab monotherapy. The other patients received ipilimumab monotherapy.

“Among patients (n=109) with BRAF wide-type melanoma, the Regimen demonstrated a significantly superior response rate of 60% vs. Yervoy [ipilimumab] alone, 11%. Seventeen percent of patients experienced a complete response in the BRAF wide-type population. Partial responses were seen in 43% of the Regimen group and 11% of the Yervoy monotherapy group,” according to the manufacturer.

Jedd D. Wolchok, MD, PhD, chief of Melanoma and Immunotherapeutics Service, Department of Medicine and Ludwig Center at Memorial Sloan Kettering Cancer Center, considered the approval “a step forward for the melanoma community, providing hope for patients with metastatic melanoma.”

Tim Turnham, executive director of the Melanoma Research Foundation, agreed with Wolchok’s sentiment. “We are currently witnessing a turning point in cancer history, based on the significant impact immune-oncology is making in the lives of patients with metastatic melanoma. Today’s approval of the first Regimen of two immune-oncology agents, Opdivo and Yervoy, is an exciting moment for our community because it reinforces we are on a positive path forward, providing new approaches which translate into meaningful results for patients.”

 

There are some safety concerns with the Regimen treatment as Yervoy can result in severe and fatal immune-mediated adverse reactions, including enterocolitis, hepatitis, dermatitis (including toxic epidermal necrolysis), neuropathy, and endocrinopathy. The safety information noted that these most severe adverse events happened during initial treatment, but in some cases did occur months after Yervoy was discontinued. Patients need to be monitored carefully, according to Wolchok, as reported by The Wall Street Journal.

Lung cancer treatment

Pembrolizumab (Keytruda, Merck) was approved by the FDA for the treatment of patients with advanced NSCLC, whose disease progressed following other treatments and with tumors expressing the protein, PD-L1. The drug is approved for use with a companion diagnostic, the PD-L1 IHC 22C3 pharmDx test.

Last year pembolizumab was approved for the treatment of patients with advanced melanoma following treatment with ipilimumab.

“Our growing understanding of underlying molecular pathways and how our immune system interacts with cancer is leading to important advances in medicine,” said Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluaton and Research. “Today’s approval of Keytruda gives physicians the ability to target specific patients who may be most likely to benefit from this drug.”

Pembrolizumab’s expanded indication for advanced NSCLC was based on study of a subgroup of 61 patients who were part of a larger multicenter, multi-part study. The patients had advanced NSCLC that had progressed following chemotherapy, and they had PD-L1 positive tumors. The outcome measures were based on the complete and partial reduction in tumor size. In 41% of patients receiving pembrolizumab, tumors shrank and were stable for 2.1 to 9.1 months.

The most common severe adverse effects from pembolizumab included immune-mediated effects of the lungs, colon, and hormone-producing glands. Uncommon immune-related side effects were rash and vasculitis, the FDA noted.