In a significant development for cervical cancer treatment, Health Canada has given the green light to the combination of pembrolizumab (Keytruda) and chemoradiotherapy (CRT) for patients diagnosed with International Federation of Gynecology and Obstetrics (FIGO) 2014 stage III to IVA cervical cancer. This approval follows an announcement by the drug’s developer, Merck, in a recent press release.
The decision by Health Canada is supported by data from the phase 3 KEYNOTE-A18 trial (NCT04221945). In this trial, researchers evaluated the effectiveness of pembrolizumab plus CRT against placebo plus CRT in patients with locally advanced cervical cancer. The results were remarkable.
Across the entire study population, the combination with pembrolizumab led to statistically significant improvements in both 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).
A subgroup analysis provided further insights. Among 459 patients with FIGO 2014 stage IB2 to IIB cervical cancer, the estimated hazard ratios (HRs) were 0.91 (95% CI, 0.63 – 1.32) for PFS and 0.89 (95% CI, 0.55 – 1.44) for OS.
This indicates that the overall improvements in efficacy were mainly driven by the outcomes of patients with more advanced disease. In contrast, among the 599 patients with FIGO 2014 stage III to IVA disease, the pembrolizumab regimen showed clear benefits, improving PFS (HR, 0.59; 95% CI, 0.43 – 0.81) and OS (HR, 0.58; 95% CI, 0.40 – 0.85).
However, like any treatment, the pembrolizumab arm in the trial also had its share of treatment-related adverse effects (TRAEs) among patients with FIGO 2014 stage III to IVA disease. Common TRAEs included anemia, diarrhea, nausea, decreases in white blood cell count, neutrophil count, vomiting, platelet count decreases, and hypothyroidism.
Shannon Salvador, MD, a gynecologic oncologist at the Jewish General Hospital and President of the Society of Gynecologic Oncology of Canada, emphasized the importance of this approval. “The approval of [pembrolizumab/CRT] is a crucial addition to the treatment of gynecological cancers. It has shown a statistically significant improvement in [OS] and [PFS] in patients with FIGO 2014 Stage III to IVA [cervical cancer]. This recent approval offers another therapeutic option for patients in this important disease area,” she stated in the press release.
The multicenter, double-blind, phase 3 KEYNOTE-A18 trial involved 1060 patients with newly diagnosed locally advanced squamous cell adenocarcinoma or adenocarcinoma of the cervix. These patients had either FIGO 2014 stage IB2 to IIB disease with positive lymph nodes or stage III to IVA disease, regardless of nodal status.
The patients were randomly assigned, on a 1:1 basis, to receive either pembrolizumab at 200 mg intravenously every 3 weeks for 5 cycles or a matched placebo. Both groups also received concurrent cisplatin at 40 mg/m² intravenously weekly, radiotherapy with external beam radiotherapy (EBRT) followed by brachytherapy, and maintenance with either pembrolizumab at 400 mg intravenously or placebo every 6 weeks.
The primary end points of the trial were PFS per RECIST v1.1 criteria, as determined by investigator assessment, and OS. Secondary end points included PFS per blinded independent central review, complete response rate, objective response rate, quality of life, and adverse events (AEs).
Eligibility for the trial required patients to be 18 years or older, with histologically confirmed squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma of the cervix.
They should not have received prior definitive surgery, radiation, or systemic therapy for cervical cancer. Other criteria included having an ECOG performance status of 0 or 1 within 7 days of starting study treatment, radiographically evaluable disease per RECIST v1.1 guidelines, and adequate organ function within 7 days of initiating treatment.
Notably, the FDA had already approved pembrolizumab plus EBRT, concurrent chemotherapy, and brachytherapy for those with FIGO stage III to IVA cervical cancer in January 2024, also based on data from the KEYNOTE-A18 trial.
André Galarneau, PhD, executive director and vice president of the Oncology Business Unit at Merck Canada, concluded, “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 affected by this disease.”
This approval is expected to offer new hope to patients in Canada struggling with FIGO 2014 stage III to IVA cervical cancer, providing them with an additional, potentially life – extending treatment option.
READ MORE
Can You Get Cervical Cancer Without an HPV Infection?
