Pembrolizumab Combo Receives Canadian Approval in Cervical Cancer

The FDA approved pembrolizumab plus EBRT, concurrent chemotherapy, and brachytherapy for those with FIGO stage III to IVA cervical cancer in January 2024 based on data from the KEYNOTE-A18 trial.

Health Canada has approved pembrolizumab (Keytruda) plus chemoradiotherapy (CRT) for patients with International Federation of Gynecology and Obstetrics (FIGO) 2014 stage III to IVA cervical cancer, according to a press release from the developer, Merck.¹

Supporting data for the Canadian approval came from the phase 3 KEYNOTE-A18 trial (NCT04221945), in which investigators assessed the efficacy of pembrolizumab plus CRT vs placebo plus CRT among those with locally advanced cervical cancer. Across the overall population, the pembrolizumab combination produced statistically significant improvements in progression-free survival (PFS; HR, 0.70; 95% CI, 0.55-0.89; P = .002) and overall survival (OS; HR, 0.67; 95% CI, 0.50-0.90; P = .004).

In a subgroup analysis including 459 patients with FIGO 2014 stage IB2 to IIB cervical cancer, the estimated HRs were 0.91 (95% CI, 0.63-1.32) for PFS and 0.89 (95% CI, 0.55-1.44) for OS, which suggested that the efficacy improvements reported in the overall population were primarily associated with outcomes among those with later-stage disease. Among 599 patients with FIGO 2014 stage III to IVA disease, the pembrolizumab regimen improved PFS (HR, 0.59; 95% CI, 0.43-0.81) and OS (HR, 0.58; 95% CI, 0.40-0.85).

The most common treatment-related adverse effects (AEs) among patients with FIGO 2014 stage III to IVA disease in the pembrolizumab arm of the trial included anemia, diarrhea, nausea, white blood cell count decreases, neutrophil count decreases, vomiting, platelet count decreases, and hypothyroidism.

“The approval of [pembrolizumab/CRT] is an important addition to the treatment of gynecological cancers, as it has demonstrated a statistically significant improvement in [OS] and [PFS] in patients with FIGO 2014 stage III to IVA [cervical cancer],” Shannon Salvador, MD, gynecologic oncologist at the Jewish General Hospital and president of the Society of Gynecologic Oncology of Canada, stated in the press release.¹ “This recent approval adds another therapeutic option for patients in an important disease space.”

The multicenter, double-blind, phase 3 KEYNOTE-A18 trial included 1060 patients with newly diagnosed locally advanced squamous cell adenocarcinoma or adenocarcinoma of the cervix defined as FIGO 2014 stage IB2 to IIB disease with positive lymph nodes or stage III to IVA disease with any nodal status. Patients were randomly assigned 1:1 to receive pembrolizumab at 200 mg intravenously every 3 weeks for 5 cycles or matched placebo plus concurrent cisplatin at 40 mg/m² intravenously weekly and radiotherapy with external beam radiotherapy (EBRT) followed by brachytherapy and maintenance with pembrolizumab at 400 mg intravenously or placebo every 6 weeks.

The trial’s primary end points were PFS per RECIST v1.1 criteria based on investigator assessment and OS.² Secondary end points included PFS per blinded independent central review, complete response rate, objective response rate, quality of life, and AEs.

Patients 18 years or older with histologically confirmed squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma of the cervix and no prior definitive surgery, radiation, or systemic therapy for cervical cancer were eligible for enrollment in the trial. Other eligibility criteria included having an ECOG performance status of 0 or 1 within 7 days of beginning study treatment, radiographically evaluable disease per RECIST v1.1 guidelines, and adequate organ function within 7 days of initiating treatment.

The FDA approved pembrolizumab plus EBRT, concurrent chemotherapy, and brachytherapy for those with FIGO stage III to IVA cervical cancer in January 2024 based on data from the KEYNOTE-A18 trial.³

“This approval marks a pivotal moment for patients, as it represents the first indication in Canada for [pembrolizumab] in combination with [CRT]. Reaffirming our commitment to cervical cancer, we are eager to continue expanding treatment options for patients impacted by this disease,” André Galarneau, PhD, executive director and vice president of the Oncology Business Unit at Merck Canada, concluded.¹

References

1. Health Canada approves KEYTRUDA for the treatment of adult patients with FIGO 2014 stage III-IVA cervical cancer, in combination with chemoradiotherapy (CRT). News release. Merck. July 21, 2025. Accessed July 22, 2025. https://tinyurl.com/5csn8d3z
2. Study of chemoradiotherapy with or without pembrolizumab (MK-3475) for the treatment of locally advanced cervical cancer (MK-3475-A18/​KEYNOTE-A18/​ENGOT-cx11/​GOG-3047). ClinicalTrials.gov. Updated January 22, 2025. Accessed July 22, 2025. https://tinyurl.com/y45vz4px
3. FDA approves pembrolizumab with chemoradiotherapy for FIGO 2014 stage III-IVA cervical cancer. FDA. January 12, 2024. Accessed July 22, 2025. https://tinyurl.com/367pbeta