FDA Approves Pembrolizumab With Chemoradiotherapy for FIGO 2014 Stage III-IVA Cervical Cancer

FDA Approves Pembrolizumab With Chemoradiotherapy for FIGO 2014 Stage III-IVA Cervical Cancer

The FDA has approved pembrolizumab (Keytruda) with chemoradiotherapy for the treatment of patients with FIGO 2014 stage III to IVA cervical cancer.

This approval was based on findings from the KEYNOTE-A18 trial (NCT04221945), in which researchers enrolled 1060 patients with cervical cancer who were not previously treated with definitive surgery, systemic therapy, or radiation. Of note, this trial included 596 patients with FIGO 2014 stage III to Iva disease and 462 patients with FIGO 2014 stage IB2 to IIB node-positive disease, according to a statement from the FDA.

Patients in the KEYNOTE-A18 (NCT04221945) trial were randomized 1:1 to receive 200 mg of pembrolizumab or placebo every 3 weeks for 5 cycles plus chemoradiotherapy, followed by 400 mg of pembrolizumab or placebo every 6 weeks for 15 cycles. The chemoradiotherapy regimen used in this trial included 40 mg/m2 of intravenous cisplatin weekly for 5 cycles, with an option to administer a sixth cycle, and external beam radiation therapy, followed by brachytherapy. Randomization was stratified by stage, planned type of external beam radiation therapy, and planned total radiotherapy response.

Researchers analyzed several major efficacy outcome measures including progression-free survival (PFS), assessed by the investigator by RECIST v1.1 or by histopathologic confirmation, and overall survival (OS).

There was a statistically significant PFS improvement in the overall population, according to the FDA’s statement. An exploratory subgroup analysis in patients with FIGO 2014 stage III to IVA disease demonstrated a PFS hazard ratio (HR) estimate of 0.59 (95% CI, 0.43-0.82). In addition, 21% of patients assigned pembrolizumab had a PFS event compared with 31% of patients assigned placebo.

In an exploratory analysis of patients with FIGO 2014 stage IB2 to IIB disease, the HR estimate for PFS was 0.91 (95% CI, 0.63-1.31), which indicated that the improvement in PFS in the overall population was driven by patients with FIGO 2014 stage III to IVA disease.

Data regarding OS were not mature when PFS was analyzed, according to the statement.

The most common adverse reactions related to pembrolizumab plus chemoradiotherapy, occurring in at least 10% of patients in the trial, included diarrhea, nausea, urinary tract infection, vomiting, hypothyroidism, fatigue, decreased appetite, constipation, abdominal pain, weight loss, hyperthyroidism pyrexia, rash, dysuria, and pelvic pain.

The dosing regimen recommended for pembrolizumab is 200 mg intravenously every 3 weeks or 400 mg intravenously every 6 weeks until unacceptable toxicity, disease progression, or for up to 24 months, according to the statement. Pembrolizumab should be given before chemoradiotherapy if administered on the same day.

Reference

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