KEYNOTE-826 Regimen Improves Survival in Persistent, Recurrent, or Metastatic Cervical Cancer

The combination of the anti-PD-1/PD-L1 therapy pembrolizumab (Keytruda) with the platinum-based chemotherapy regimens paclitaxel plus cisplatin or paclitaxel plus carboplatin administered with or without bevacizumab (Avastin) improved both progression-free (PFS) and overall survival (OS) in patients with persistent, recurrent, or metastatic cervical cancer, meeting the primary end point of the phase 3 KEYNOTE-826 trial.1

Achievement of the co-primary end points was announced in a press release from Merck, the developer of pembrolizumab, where the company also reported that the results will be presented during an upcoming medical meeting and shared with regulatory authorities. The results will serve as confirmatory evidence to support the accelerated approval of pembrolizumab for the second-line treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-1, as determined by an FDA-approved test.

“Despite progress with prevention and screening, cervical cancer continues to be a major health problem, often affecting younger and middle-aged women,” said Roy Baynes, PhD, senior vice president, head of global clinical development, and chief medical officer, Merck Research Laboratories. “Women diagnosed with metastatic cervical cancer have a particularly poor prognosis, and there is an urgent need for new treatment options. KEYNOTE-826 is the first study to show positive results for immunotherapy in first-line persistent, recurrent, or metastatic cervical cancer, and we look forward to sharing these findings at an upcoming congress and discussing them with regulatory authorities.

KEYNOTE-826 was conducted based on the modest OS benefit observed with the bevacizumab and chemotherapy in comparison with chemotherapy only. A 2017 study (NCT00803062) showed a median OS of 16.8 months with bevacizumab plus chemotherapy versus 13.3 months with chemotherapy alone (HR, 0.77; 95% CI, 0.62-0.95; P = .007). It was hypothesized that pembrolizumab could enhance the benefit of chemotherapy in patients with PD-L1-positive cervical as was previously demonstrated in the phase 2 KEYNOTE-158 trial (NCT02628067), which explored the strategy as treatment of patients with previously treated, advanced non colorectal microsatellite-high and mismatch repair-deficient cancer.2

The KEYNOTE-826 is designed to investigate the efficacy and safety of pembrolizumab plus platinum-based chemotherapy with or without bevacizumab in patients with persistent, recurrent, or metastatic cervical cancer. The secondary end points of the study include objective response rate, duration of response, PFS at month 12, PFS per RECIST v1.1, the number of patients with adverse events (AEs), the number of patients with serious AEs, the percentage of patients who experience immune-related AEs, the number of treatment discontinuations in the study, and the number of patients with a 10-point change from baseline in quality of life.

Patients are eligible to enroll given they have measurable disease per RECISTs v1.1, an ECOG performance score of 0 or 1, adequate organ function, and archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion. Pregnant patients as well as those with central nervous system metastases, another malignancy, or comorbidities that may interfere with study treatment were excluded from the study.

_References:

_{1. Merck announces phase 3 KEYNOTE-826 trial met dual primary endpoints of overall survival (OS) and progression-free survival (PFS) in patients with persistent, recurrent or metastatic cervical cancer. News release. Merck. June 22, 2021. Accessed June 22, 2021. https://bit.ly/3gM2rVy}

_{2. Fujiwara K, Shapira-Frommer R, Alexandra J, et al. KEYNOTE-826: A phase III randomized study of chemotherapy with or without pembrolizumab for first-line treatment of persistent, recurrent, or metastatic cervical cancer. Ann Oncol. 2019. 30(9); IX89-IX90. doi: 10.1093/annonc/mdz426.040}