Pembrolizumab with chemoradiotherapy is approved by the USFDA for FIGO 2014 Stage III-IVA cervical cancer

The Food and Drug Administration authorized pembrolizumab (Keytruda, Merck) in combination with chemoradiotherapy (CRT) for patients with FIGO 2014 Stage III-IVA cervical cancer on January 12, 2024.

A study called KEYNOTE-A18 (NCT04221945) looked at how well it worked. It was a multicenter, randomized, double-blind, placebo-controlled trial with 1060 cervical cancer patients who had not previously had surgery, radiation, or systemic therapy. There were 596 people in the trial with FIGO 2014 Stage III–IVA disease and 462 people with FIGO 2014 Stage IB–IIB disease who had node-positive illness.

Participants were randomly assigned to receive either pembrolizumab 200 mg or a placebo every 3 weeks for 5 cycles along with CRT. Every six weeks for 15 cycles, pembrolizumab 400 mg or a placebo came after this. The CRT regimen included cisplatin at a dose of 40 mg/m2 given intravenously once a week for 5 cycles, with the possibility of an additional 6th cycle, as well as external beam radiation therapy (EBRT) and brachytherapy. Randomization was stratified based on the intended kind of external beam radiation therapy (EBRT), cancer stage, and projected total irradiation dose.

The primary efficacy indicators included progression-free survival (PFS) evaluated by the investigator based on RECIST v1.1 criteria or histopathologic confirmation, and overall survival (OS). The trial showed a statistically significant enhancement in progression-free survival (PFS) throughout the entire group. An exploratory subgroup analysis was conducted on 596 patients with FIGO 2014 Stage III-IVA illness. The PFS hazard ratio estimate was 0.59 (95% CI: 0.43, 0.82). In the pembrolizumab arm, 21% of patients experienced a PFS event compared to 31% in the placebo arm. An exploratory subgroup analysis was conducted on 462 patients with FIGO 2014 Stage IB2-IIB disease. The PFS HR estimate was 0.91 (95% CI: 0.63, 1.31), suggesting that the PFS improvement in the entire population was mainly seen in patients with FIGO 2014 Stage III-IVA disease. The OS data were insufficiently developed when the PFS analysis was conducted.

Patients who were given pembrolizumab along with chemoradiotherapy most often experienced side effects like nausea, diarrhea, vomiting, urinary tract infections, fatigue, hypothyroidism, constipation, loss of appetite, weight gain, abdominal pain, pyrexia, hyperthyroidism, dysuria, rash, and pelvic pain.

The suggested dose schedule for pembrolizumab is 200 mg administered intravenously every 3 weeks or 400 mg intravenously every 6 weeks, continuing until disease advancement, intolerable side effects, or for a maximum of 24 months. Administer pembrolizumab before chemoradiotherapy if given on the same day.