Skip to main content

FDA Approves Keytruda Regimen for Recurrent or Metastatic Cervical Cancer

November 2021, Vol 11, No 11

On October 13, 2021, the FDA approved a new indication for the PD-1 inhibitor pembrolizumab (Keytruda; Merck) for use in combination with chemotherapy, with or without bevacizumab (Avastin; Genentech), for the treatment of patients with persistent, recurrent, or metastatic cervical cancer whose tumors express PD-L1 (combined positive score ≥1) as determined by an FDA-approved test.

“Cervical cancer more commonly affects younger women and certain women of color in the US, and unfortunately, women diagnosed with persistent, recu1rrent or metastatic cervical cancer often have a low survival rate,” said Bradley Monk, MD, FACOG, FACS, Medical Director, Gynecologic Oncology Research, US Oncology, and Director and Professor, Obstetrics and Gynecology, University of Arizona College of Medicine, Tucson, and Creighton University School of Medicine at St. Joseph’s Hospital and Medical Center, Phoenix, AZ, in a press release. “There have been no first-line approvals for women with persistent, recurrent, or metastatic cervical cancer in the past 7 years. I am excited for today’s approval of a new combination with Keytruda, which offers a new treatment option for appropriate patients.”

This new approval is based on the phase 3, multicenter, randomized, double-blind KEYNOTE-826 trial of pembrolizumab plus chemotherapy (paclitaxel plus cisplatin or paclitaxel plus carboplatin) with or without bevacizumab compared with the same chemotherapy regimens with or without bevacizumab.

The study included 617 patients with persistent, recurrent, or first-line metastatic cervical cancer who had not received chemotherapy. Participants were randomized in a 1:1 ratio to receive pembrolizumab 200 mg plus chemotherapy, in the form of paclitaxel and cisplatin or paclitaxel and carboplatin with or without bevacizumab, or placebo plus chemotherapy with or without bevacizumab. Pembrolizumab was continued until progressive disease, intolerable toxicity, or 24 months of treatment. Patients were permitted to enroll irrespective of PD-L1 expression status.

The main efficacy end point measures were overall survival (OS) and progression-free survival. Secondary end point measures included overall response rate (ORR) and DOR. Pembrolizumab plus chemotherapy with or without bevacizumab demonstrated superior OS (hazard ratio, 0.64; 95% CI, 0.50-0.81; P = .0001) and progression-free survival (hazard ratio, 0.62; 95% CI, 0.50-0.77; P <.0001) compared with chemotherapy with or without bevacizumab in patients whose tumors expressed PD-L1 (combined positive score ≥1). In addition, more patients responded to pembrolizumab plus chemotherapy with or without bevacizumab than to chemotherapy with or without bevacizumab, with an ORR of 68% (95% CI, 62-74) versus 50% (95% CI, 44-56), respectively. Among patients who responded, the median DOR was 18.0 months for pembrolizumab plus chemotherapy with or without bevacizumab, and 10.4 months for chemotherapy with or without bevacizumab.

The most common (≥20%) AEs were peripheral neuropathy, alopecia, anemia, fatigue/asthenia, nausea, neutropenia, diarrhea, hypertension, thrombocytopenia, constipation, arthralgia, vomiting, urinary tract infection, rash, leukopenia, hypothyroidism, and decreased appetite.

The recommended pembrolizumab dose is 200 mg every 3 weeks or 400 mg every 6 weeks until disease progression, unacceptable toxicity, or up to 24 months.

Related Items