FDA Approves Pembrolizumab Combination Therapy for Cervical Cancer


Pembrolizumab (Keytruda) approved by FDA in combination with chemotherapy, with or without bevacizumab (Avastin), in patients with persistent, recurrent, or metastatic cervical cancer.

The FDA has approved pembrolizumab (Keytruda) in combination with chemotherapy, with or without bevacizumab (Avastin), in patients with persistent, recurrent, or metastatic cervical cancer whose tumors have a programmed death-ligand 1 (PD-L1) combined positive score (CPS) of 1 or higher determined by an FDA-approved test.1

Further, the FDA granted regular approval to pembrolizumab monotherapy for patients with recurrent or metastatic cervical cancer whose disease progressed on or after chemotherapy with tumors that have a PD-L1 CPS of 1 or greater 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, recurrent or metastatic cervical cancer often have a low survival rate,” said Bradley Monk, MD, medical director of US Oncology Research Gynecology Program, 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.”

In June 2018, the FDA granted accelerated approval to pembrolizumab in the second-line treatment of patients with recurrent or metastatic cervical cancer whose disease progressed on or after chemotherapy and whose tumors express PD-L1.2 The approved was based on data from 98 patients with recurrent or metastatic cervical cancer enrolled to a single cohort in the phase 2 KEYNOTE-158 trial.

At a median follow-up of 11.7 months, pembrolizumab produced an overall response rate (ORR) of 14.3% (95% CI, 7.4-24.1) in 77 patients with PD-L1 positivity who were previously treated with at least 1 line of chemotherapy in the metastatic setting. The median duration of response (DOR) was not reached. Ninety-one percent of responders experienced a response that lasted for 6 months or longer.3

Continued approval for this indication was contingent upon verification and description of clinical benefit in confirmatory trials. The multicenter, randomized, double-blind, placebo-controlled, phase 3 KEYNOTE-826 trial was used as the confirmatory trial for the approval. A total of 617 patients with persistent, recurrent, or first-line metastatic cervical cancer who had not received chemotherapy were enrolled irrespective of PD-L1 expression status.

Study participants were randomized 1:1 to receive either pembrolizumab 200 mg plus paclitaxel and cisplatin or paclitaxel and carboplatin, with or without bevacizumab or placebo, plus chemotherapy with or without bevacizumab. Pembrolizumab was continued until disease progression, intolerable toxicity, or 24 months of treatment.

The primary efficacy outcome measures were investigator-assessed overall survival (OS) and progression-free survival (PFS) per RECIST v1.1 criteria, which was modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. Additional outcome measures of interest included ORR and DOR.

Among patients with tumors with a PD-L1 CPS of 1 or higher (n = 548), the median OS was not yet reached (95% CI, 19.8–not reached) in the pembrolizumab cohort compared with 16.3 months (95% CI, 14.5-19.4) in the placebo cohort (HR 0.64; 95% CI, 0.50-0.81; 1-sided P = .0001).

Further, median PFS was 10.4 months (95% CI, 9.70-12.3) in the pembrolizumab cohort compared with 8.2 months (95% CI, 6.3-8.5) in the placebo cohort (HR 0.62; 95% CI, 0.50-0.77; 1-sided < .0001). The ORRs were 68% (95% CI, 62%-74%) and 50% (95% CI, 44%-56%), respectively, with a median DOR of 18.0 and 10.4 months, respectively.

Adverse events that occurred in 20% or more of patients administered pembrolizumab, chemotherapy, and bevacizumab included peripheral neuropathy, alopecia, anemia, fatigue/asthenia, nausea, neutropenia, diarrhea, hypertension, thrombocytopenia, constipation, arthralgia, vomiting, urinary tract infection, rash, leukopenia, hypothyroidism, and decreased appetite.

“Today’s news is a meaningful step forward, as it offers a new therapeutic option for these patients and reinforces the role of Keytruda in treating certain types of cervical cancers, with a second indication for the disease,” said Roy Baynes, MD, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories, in a press release. “The data showing a 36% reduction in the risk of death are compelling, and this approval brings an important new first-line treatment option to women with persistent, recurrent or metastatic cervical cancer whose tumors express PD-L1 (CPS ≥1).”


  1. FDA approves pembrolizumab combination for the first-line treatment of cervical cancer. News release. FDA. October 13, 2021. Accessed October 13, 2021. https://bit.ly/3lE3vNS
  2. FDA approves Merck’s KEYTRUDA (pembrolizumab) for previously treated patients with recurrent or metastatic cervical cancer whose tumors express PD-L1 (CPS greater than or equal to 1). News release. Merck. June 12, 2018. Accessed October 13, 2021. https://bit.ly/3zPQw0e
  3. Pembrolizumab. Prescribing information. Merck; 2014. Accessed October 31, 2021. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/125514s034lbl.pdf
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