FDA Approves Pembrolizumab With Chemotherapy for PD-L1+ Recurrent or Metastatic Cervical Cancer


Pembrolizumab is now FDA approved in combination with chemotherapy and with or without bevacizumab, for the treatment of patients with persistent, recurrent or metastatic cervical cancer whose tumors express PD-L1.

The FDA has granted approval to pembrolizumab (Keytruda) in combination with chemotherapy and with or without bevacizumab (Avastin), for the treatment of patients with persistent, recurrent or metastatic cervical cancer whose tumors express PD-L1 with a combined positive score (CPS) ≥1, as determined by an FDA-approved test, according to an FDA issued press release.1

A regular approval was simultaneously granted by the FDA to single-agent pembrolizumab, for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test. This approval follows an accelerated approval for this indication granted in June 2018 with the companion diagnostic PD-L1 IHC 22C3 pharmDx.

Results from the phase 3 multicenter, randomized, double-blind, placebo-controlled trial (KEYNOTE-826; NCT03635567) support the FDA approval of pembrolizumab/chemotherapy and pembrolizumab alone for patients with recurrent or metastatic cervical cancer with PD-L1 expression. Results from the study were recently presented during the European Society of Medical Oncology Congress 2021.1,2

KEYNOTE-826 showed that adding pembrolizumab to chemotherapy with or without bevacizumab led to a statistically significant and clinically meaningful improvement in overall survival (OS), and progression-free survival (PFS) in women with persistent, recurrent, or metastatic cervical cancer.2

The study included 617 patients with persistent, recurrent, or metastatic cervical cancer not amenable to curative treatment who did not receive prior systemic chemotherapy and had an ECOG performance status of 0 or 1. Patients were randomized 1:1 to either pembrolizumab 200 mg given intravenously (IV) every 3 weeks (Q3W) for up to 35 cycles in combination with paclitaxel plus cisplatin or carboplatin iv Q3W for up to 6 cycles, and with or without bevacizumab 15 mg/kg IV Q3W. In the control arm, patients received matching placebo, paclitaxel, cisplatin, carboplatin, and in some cases, bevacizumab.

The coprimary end points of KEYNOTE-826 were OS and PFS per RECIST v1.1 and by investigator assessment. The secondary end points included objective response rate (ORR), duration of response (DOR), 12-month PFS rate, and safety. The study also looked at the exploratory end point of patient-reported outcomes.

Patients were stratified by presence of absence of metastases, high versus low PD-L1 expression, and whether or not they receive bevacizumab.

At a median follow-up of 22.0 months (range, 15.1-29.4), the 12-month PFS rate in in patients with a PD-L1 CPS ≥ 1 was 45.5% (95% CI, 39.2%-51.5%) with the pembrolizumab combination compared with 34.1% (95% CI, 28.3%-40.0%) with the placebo combination (HR, 0.62; 95% CI, 0.50-0.77; P <.001). Those with a PD-L1 CPS of ≥10 had a 12-month PFS rate of 44.6% (95% CI, 36.3%-52.5%) with pembrolizumab/chemotherapy compared with 33.5% (95% CI, 25.9%-41.2%) with the control combination (HR, 0.58; 95% CI, 0.44-0.77; P <.00).

The 24-month OS rate in the low PD-L1 CPS group treated with pembrolizumab plus chemotherapy was 53.0% (95% CI, 46.0%-59.4%) compared with 41.7% (95% CI, 34.9%-48.2%) with the control (HR, 0.64; 95% CI, 0.50-0.81; P <.001. Among patients with ahigh PD-L1 CPS, the 24-month OS rate was 50.4% (95% CI, 43.8%-56.6%) with the experimental combination compared with 40.4% (95% CI, 34.0%-46.6%) with the control (HR, 0.67; 95% CI, 0.54-0.84; P <.001)

The ORR observed with the pembrolizumab combination was in patients with a PD-L1 cPS ≥ 1 was 68.1% (95% CI, 62.2%-73.6%) compared with 50.2% (95% CI, 44.1%-56.2%) among patients treated with the placebo and chemotherapy. The median DOR was 18.0 months (range, 1.3+ to 24.2+) in the pembrolizumab arm compared with only 10.4 months (range, 1.5+ to 22.0+) in the placebo/chemotherapy arm. In patients with a PD-L1 CPS ≥ 10, the ORR rate in the pembrolizumab arm was 65.5% (95% CI, 61.8%-76.7%) compared with 49.1% (95% CI, 41.1%-57.1%). The median DOR was 21.1 months (range 1.3+ to 24.2+) with pembrolizumab/chemotherapy compared with 9.4 months (range 2.1+ to 21.5+) with placebo/chemotherapy.

According to the FDA, peripheral neuropathy, alopecia, anemia, fatigue/asthenia, nausea, neutropenia, diarrhea, hypertension, thrombocytopenia, constipation, arthralgia, vomiting, urinary tract infection, rash, leukopenia, hypothyroidism, and decreased appetite are the most common adverse event observed with the combination of pembrolizumab, chemotherapy, and bevacizumab. The FDA recommends that pembrolizumab be dosed at 200 mg every 3 weeks or 400 mg every 6 weeks until disease progression, unacceptable toxicity, or up to 24 months.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/3mSI62v

2. Colombo N Dubot C, Lorusso D, et al. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for persistent, recurrent, or metastatic cervical cancer: Randomized, double-blind, phase III KEYNOTE-826 study. Presented at: 2021 ESMO Congress; September 16-21, 2021; virtual. Abstract LBA2_PR.

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