FDA Approves Pembrolizumab for Advanced Merkel Cell Carcinoma

Roxanne Nelson, RN, BSN

December 20, 2018

The US Food and Drug Administration (FDA) has approved pembrolizumab (Keytruda, Merck), a programmed cell death–ligand-1 (PD-L1) inhibitor, for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC).

A rare and aggressive neuroendocrine skin cancer, MCC is often fatal. MCC is diagnosed in approximately 1600 people in the United States each year, although it has been reported that the incidence is rising. Although most patients present with localized tumors that can be treated with surgical resection, approximately half of all patients will experience recurrence, and more than 30% will eventually develop metastatic disease.

Last year, another PD-L1 inhibitor, avelumab (Bavencio, EMD Serono) received FDA approval for MCC, making it the first approved treatment for this disease.

Now pembrolizumab will be added to the armamentarium of treatments for MCC.

High Response Rate

The approval was based on findings from the Cancer Immunotherapy Trials Network Protocol 9 (CITN-09), also known as KEYNOTE-017, a multicenter, nonrandomized, open-label phase 2 clinical trial. In that trial, half of the patients with advanced MCC showed a response to treatment. The data were presented earlier this year at the annual meeting of the American Society of Clinical Oncology (ASCO).

The cohort included 50 patients with recurrent locally advanced or metastatic MCC who had not received prior systemic therapy for their advanced disease. Patients received pembrolizumab 2 mg/kg every 3 weeks. The major efficacy outcome measures were overall response rate (ORR) and response duration, assessed by blinded independent central review per RECIST 1.1. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and duration of response.

The ORR was 56%; the complete response rate was 24%; and the partial response rate was 32%. The median response duration was not reached, but of the 28 patients who achieved a response, the duration of response was greater than 6 months for 96%. In addition, for more than half of patients who responded to treatment (54%), the duration of response was 12 months or longer.

The median PFS was not reached. OS at 18 months was 68%, which compares favorably to historical rates with chemotherapy. Median OS was also not reached, and among the 21 confirmed patients who demonstrated a response, the median response duration was also not reached (range, 3.9+ to 25.6+ months).

"KEYNOTE-017 represents the longest observation to date of patients with advanced Merkel cell carcinoma receiving anti-PD-1 therapy in the first-line setting and demonstrated durable tumor control in these patients," said Scot Ebbinghaus, MD, vice president of clinical research at Merck Research Laboratories, in a release. "We look forward to working closely with the FDA throughout the review process and to bringing Keytruda to patients with Merkel cell carcinoma."

Pembrolizumab has already been approved for nine cancer types, including melanoma, lung cancer, head and neck cancer, Hodgkin lymphoma, urothelial carcinoma, gastric cancer, cervical cancer, primary mediastinal large B-cell lymphoma. It has also been approved for microsatellite instability–high cancers.

Pembrolizumab received accelerated approval for this indication on the basis of tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

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