FDA Approves Pembrolizumab for Previously Treated Recurrent or Metastatic PD-L1–Expressing Cervical Cancer


On June 12, the U.S. Food and Drug Administration (FDA) approved pembrolizumab (Keytruda) for the treatment of patients with recurrent or metastatic cervical cancer and disease progression on or after chemotherapy whose tumors express programmed cell death ligand 1 (PD-L1) [Combined Positive Score (CPS) ≥ 1], as determined by an FDA-approved test.

This indication is approved under the FDA’s accelerated approval regulations based on 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.

“Even with the many advances observed across gynecologic cancers, new treatment options have been lacking for previously treated patients with advanced cervical cancer,” said Bradley Monk, MD, oncologist with Arizona Oncology, Medical Director of US Oncology Research Gynecology Program, and Professor of Obstetrics and Gynecology at the University of Arizona College of Medicine and Creighton University School of Medicine. “The approval of pembrolizumab in this indication is important news—and as an oncologist, it is exciting to see a much-needed option made available to these patients.”


The efficacy of pembrolizumab was investigated in 98 patients with recurrent or metastatic cervical cancer enrolled in a single cohort (cohort E) in the KEYNOTE-158 study, a multicenter, nonrandomized, open-label, multicohort trial. The trial excluded patients with autoimmune disease or a medical condition that required immunosuppression.

Patients were treated with pembrolizumab intravenously at a dose of 200 mg every 3 weeks until unacceptable toxicity or documented disease progression. Patients with initial radiographic disease progression could receive additional doses of treatment during confirmation of progression unless disease progression was symptomatic, was rapidly progressive, required urgent intervention, or occurred with a decline in performance status. Patients without disease progression could be treated for up to 24 months.

Assessment of tumor status was performed every 9 weeks for the first 12 months and every 12 weeks thereafter. The major efficacy outcome measures were objective response rate according to Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1, as assessed by blinded independent central review, and duration of response.

Among the 98 patients in cohort E, 77 (79%) had tumors that expressed PD-L1 with a CPS ≥ 1 and received at least 1 line of chemotherapy in the metastatic setting. PD-L1 status was determined using the PD-L1 IHC 22C3 pharmDx Kit. Among these 77 patients at baseline, median age was 45 years (range = 27–75 years); 81% were white, 14% Asian, and 3% black; ECOG performance status was 0 (32%) or 1 (68%); 92% had squamous cell carcinoma, 6% adenocarcinoma, and 1% adenosquamous histology; 95% had M1 disease and 5% had recurrent disease; and 35% had received 1 and 65% had received 2 or more prior lines of therapy in the recurrent or metastatic setting.

Trial Results

For the 77 patients whose tumors expressed PD-L1 with a CPS ≥ 1, the objective response rate was 14.3% (95% confidence interval [CI] = 7.4–24.1), with a complete response rate of 2.6 % and partial response rate of 11.7%. Among the 11 responding patients, median duration of response was not yet reached (range = 4.1–18.6+ months), and 91% experienced a duration of response of 6 months or longer. The median follow-up time was 11.7 months (range = 0.6–22.7 months). No responses were observed in patients whose tumors did not have PD-L1 expression (CPS < 1).

Pembrolizumab was discontinued due to adverse reactions in 8% of 98 patients (in cohort E) enrolled with recurrent or metastatic cervical cancer. Serious adverse reactions occurred in 39% of patients receiving pembrolizumab.

The most frequent serious adverse reactions reported included anemia (7%), fistula, hemorrhage, and infections [except urinary tract infections] (4.1% each). The most common adverse reactions (occurring in ≥ 20% of patients) were fatigue (43%), musculoskeletal pain (27%), diarrhea (23%), pain and abdominal pain (22% each), and decreased appetite (21%). 

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.