FDA Approves Pembrolizumab Plus Chemoradiotherapy for Patients With Stage III to IVA Cervical Cancer

On January 12, 2024, the US Food and Drug Administration (FDA) approved pembrolizumab plus chemoradiotherapy for patients with FIGO 2014 Stage III to IVA cervical cancer based on results from the multicenter, double-blind, placebo-controlled, phase 3 KEYNOTE-A18 trial.

This study enrolled 1060 patients with stage III to IVA (n = 596) and stage IB2 to IIB (n = 462), node-positive cervical cancer who did not previously receive definitive surgery, radiation, or systemic therapy. Patients were randomized on a 1-to-1 basis to receive 200 mg of pembrolizumab or placebo every 3 weeks plus weekly cisplatin for 5 cycles, external beam radiation therapy (EBRT), and brachytherapy, followed by an additional 400 mg of pembrolizumab or placebo every 6 weeks for 15 cycles. Randomization was stratified based on planned type of EBRT, disease stage, and planned total radiotherapy dose. The major efficacy measures were investigator-assessed progression-free survival (PFS) and overall survival (OS). 

At analysis, the PFS hazard ratio (HR) estimate for patients with stage III to IVA disease was 0.59. In the pembrolizumab arm 21% of patients experienced a PFS event compared to 31% of patients in the placebo arm. Among patients with IB2 to IIB disease, the PFS HR estimate was 0.91, indicating the overall PFS improvement was attributed to patients with stage III to IVA disease. OS data was not mature at the time of PFS analysis. 

The most common adverse events occurring in ≥10% of patients included nausea, diarrhea, vomiting, urinary tract infection, fatigue, hypothyroidism, constipation, decreased appetite, weight loss, abdominal pain, pyrexia, hyperthyroidism, dysuria, rash, and pelvic pain. 

The recommended dose of pembrolizumab is 200 mg every 3 weeks or 400 mg every 6 weeks until disease progression, unacceptable toxicity, or for up to 24 months. When administered on the same day as chemoradiotherapy, pembrolizumab should be administered first.

Source: 

FDA approves pembrolizumab with chemoradiotherapy for FIGO 2014 stage III-IVA cervical cancer. Published January 12, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-chemoradiotherapy-figo-2014-stage-iii-iva-cervical-cancer