FDA Approves Pembrolizumab Combination for Cervical Cancer

Cervical cancer.

The FDA has granted approval to pembrolizumab (Keytruda®, Merck) in combination with chemotherapy, with or without bevacizumab, for patients with persistent, recurrent, or metastatic cervical cancer whose tumors express programmed death-ligand 1 (PD-L1). The FDA has also granted regular approval to single-agent pembrolizumab for patients with recurrent or metastatic cervical cancer whose tumors express PD-L1, with a combined positive score of ≥1, who experienced disease progression on or after chemotherapy.

“Pembrolizumab has efficacy in PD-L1–positive metastatic or unresectable cervical cancer that has progressed during chemotherapy,” wrote Nicoletta Colombo, MD, PhD, Director of Gynecologic Cancer Medical Treatments at the European Institute of Oncology and Associate Professor of Obstetrics and Gynecology at the University of Milan-Bicocca, and colleagues, in their published results of the KEYNOTE-826 clinical trial (NCT03635567), on which the approvals were based. “We assessed the relative benefit of adding pembrolizumab to chemotherapy with or without bevacizumab.”

A total of 617 patients with persistent, recurrent, or first-line metastatic cervical cancer who had not been treated with chemotherapy enrolled in the multicenter, randomized, double-blind, placebo-controlled phase 3 trial. These patients were randomized 1:1 to receive either 200 mg pembrolizumab plus platinum-based chemotherapy with or without bevacizumab or placebo plus chemotherapy with or without bevacizumab. Pembrolizumab was administered until disease progression, unacceptable toxicity, or the completion of 24 months of treatment. Primary end points were overall survival and progression-free survival. Secondary end points were overall response rate and duration of response.

For patients with tumors expressing PD-L1, median overall survival was not reached in the pembrolizumab treatment arm, versus 16.3 months in the placebo arm. Median progression-free survival was 10.4 months in the pembrolizumab arm and 8.2 months in the placebo arm. The objective response rates were 68% in the pembrolizumab group and 50% in the placebo group, with median durations of response of 18.0 months and 10.4 months, respectively.

The most common adverse reactions occurring in at least 20% of patients treated with pembrolizumab, chemotherapy, and bevacizumab were peripheral neuropathy, alopecia, anemia, fatigue/asthenia, nausea, neutropenia, diarrhea, hypertension, thrombocytopenia, constipation, arthralgia, vomiting, urinary tract infection, rash, leukopenia, hypothyroidism, and decreased appetite.

“Progression-free and overall survival were significantly longer with pembrolizumab than with placebo among patients with persistent, recurrent, or metastatic cervical cancer who were also receiving chemotherapy with or without bevacizumab,” concluded Dr. Colombo and colleagues in their September 2021 publication in The New England Journal of Medicine.

The recommended dose of pembrolizumab is 200 mg every three weeks or 400 mg every six weeks until disease progression, unacceptable toxicity, or up to 24 months.

For More Information

Colombo N, Dubot C, Lorusso D, et al (2021). Pembrolizumab for persistent, recurrent, or metastatic cervical cancer. N Engl J Med. [Epub ahead of print] DOI:10.1056/NEJMoa2112435

Clinicaltrials.gov (2020). Efficacy and safety study of first-line treatment with pembrolizumab (MK-3475) plus chemotherapy versus placebo plus chemotherapy in women with persistent, recurrent, or metastatic cervical cancer (MK-3475-826/KEYNOTE-826). NLM identifier: NCT03635567.

Keytruda® (pembrolizumab) prescribing information (2021). Merck. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/125514s121s122lbl.pdf

US Food & Drug Administration (2021). FDA approves pembrolizumab combination for the first-line treatment of cervical cancer. Available at: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-combination-first-line-treatment-cervical-cancer

Image credit: National Cancer Institute. Licensed under public domain

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