FDA Approves Pembrolizumab Plus Chemo With or Without Bevacizumab for Frontline Cervical Cancer

October 13, 2021

The FDA has approved pembrolizumab for use in combination with chemotherapy, with or without bevacizumab, in patients with persistent, recurrent or metastatic cervical cancer whose tumors have a PD-L1 combined positive score of 1 or higher, as determined by an FDA-approved test.

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

The regulatory agency also granted regular approval to pembrolizumab as a monotherapy in patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors have a PD-L1 CPS of 1 or higher. as determined by an FDA-approved test.

In June 2018, the FDA granted an accelerated approval to pembrolizumab for the second-line treatment of patients with recurrent or metastatic cervical cancer who experienced disease progression on, or after, chemotherapy, and whose tumors express PD-L1.² The decision was based on data collected from 98 patients with recurrent or metastatic cervical cancer who were enrolled to a single cohort in the phase 2 KEYNOTE-158 trial (NCT02628067).

At a median follow-up of 11.7 months, the immunotherapy elicited an overall response rate (ORR) of 14.3% (95% CI, 7.4-24.1) in 77 patients with PD-L1 positivity who had received prior treatment with at least 1 line of chemotherapy in the metastatic setting. The median duration of response (DOR) had not yet been reached. Ninety-one percent of responders experienced a response that persisted for 6 months or longer.³

The continued approval for the indication was contingent upon verification and description of clinical benefit in confirmatory trials. The multicenter, randomized, double-blind, placebo-controlled, phase 3 KEYNOTE-826 (NCT03635567) served as the confirmatory trial for the approval.

KEYNOTE-826 enrolled a total of 617 patients with persistent, recurrent, or first-line metastatic cervical cancer who had not received chemotherapy. Notably, patients were permitted to enroll irrespective of PD-L1 expression status.

Study participants were randomized 1:1 to receive either pembrolizumab at a dose of 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.

The main efficacy outcome measures for the trial included 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 objective response rate (ORR) and duration of response (DOR).

Results showed that for 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 arm vs 16.3 months (95% CI, 14.5-19.4) in the placebo arm (HR 0.64; 95% CI, 0.50-0.81; 1-sided P = .0001).

Moreover, the median PFS was 10.4 months (95% CI, 9.70-12.3) in the pembrolizumab arm vs 8.2 months (95% CI, 6.3-8.5) in the placebo arm (HR 0.62; 95% CI, 0.50-0.77; 1-sided P < .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.

Regarding safety, the most frequent toxicities to occur in 20% or more of patients who received 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.

References

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
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
Pembrolizumab. Prescribing information. Merck; 2014. Accessed October 31, 2021. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/125514s034lbl.pdf