Bradley Monk, MD, FACOG, FACS, Gynecologic Oncologist, Arizona Oncology speaks about the ESMO 2021 Abstract #LBA2, Presidential Symposium: KEYNOTE-826: A Randomized, Double-Blind, Phase 3 Study of Pembrolizumab + Chemotherapy vs Placebo + Chemotherapy for First-Line Treatment of Persistent, Recurrent, or Metastatic Cervical Cancer.
265TiP Abstract:
Background:
Patients with advanced cervical cancer have a significant chance of death and a poor prognosis. Although adding the anti-VEGF agent bevacizumab to platinum- and taxane-based chemotherapy (CT) is associated with a modest OS benefit compared to CT alone (median OS, 16.8 vs 13.3 mo; hazard ratio, 0.77, 95 percent CI, 0.62-0.95; P = 0.007; Tewari et al. Lancet. 2017), VEGF has emerged as a therapeutic target for these patients. The PD-1 inhibitor pembrolizumab was granted accelerated approval by the US FDA for patients with PD-L1–positive (combined positive score [CPS] of > 1) cervical cancer who had progressed during or after treatment based on an ORR of 14.3 percent (95 percent CI, 7.4-24.1) in the cervical cancer cohort of KEYNOTE-158 (Chung et al. J Clin Oncol. 2019). KEYNOTE-826 (NCT03635567) is a phase 3 randomized, double-blind, international trial evaluating the effectiveness and acceptability of CT in the first-line context with or without pembrolizumab and/or bevacizumab.
Design of the experiment:
Every three weeks, eligible patients with recurrent, persistent, or metastatic cervical cancer who have not previously had CT in a recurrent or metastatic context and are not susceptible to curative therapy will be randomized 1:1 to CT + pembrolizumab 200 mg or placebo. Before randomization, the investigator will choose the CT regimen (paclitaxel 175 mg/m2 + cisplatin 50 mg/m2 or carboplatin AUC 5, with or without bevacizumab 15 mg/kg). Metastasis status at diagnosis, planned bevacizumab usage (yes/no), and tumor PD-L1 CPS (1, 1 to 10, or 10) will all be used to stratify patients. Treatment will last 35 cycles (two years) or until illness progression, intolerable toxicity, or patient withdrawal. PFS per RECIST v1.1 (evaluated by blinded independent central review) and OS are the primary objectives. ORR, the durability of response, 12-month PFS, patient-reported quality of life, and safety are secondary goals. Enrollment is open right now.
Clinical trial identification
NCT03635567.