The phase II KEYNOTE-158 basket trial evaluated single-agent pembrolizumab in patients with previously treated advanced cervical cancer.
Single-agent pembrolizumab showed durable clinical activity in patients with previously treated advanced cervical cancer enrolled on the phase II KEYNOTE-158 basket trial, and activity was higher among patients with programmed death-ligand 1 (PD-L1)–positive tumors (combined positive score [CPS] ≥1). The interim results were published in the Journal of Clinical Oncology.
The KEYNOTE-158 basket trial (ClinicalTrials.gov identifier: NCT02628067) results were first reported at the 2018 American Society of Clinical Oncology annual meeting, leading to the US Food and Drug Administration accelerated approval of single-agent pembrolizumab for the treatment of patients with recurrent or metastatic cervical cancer that progressed on or after chemotherapy and for whom tumors express PD-L1 (CPS ≥ 1).
A total of 98 advanced cervical cancer patients with previously treated disease received single-agent pembrolizumab on the basket trial. Pembrolizumab was administered at a dose of 200 mg every 3 weeks for 2 years but was stopped early if disease progression or intolerable toxicity occurred, or at the request of the physician or patient.
Patients had a median age of 46.0 years (range, 24 to 75 years) and approximately two-thirds had an Eastern Cooperative Oncology Group performance status of 1. Most patients (83.7%) had tumors that were PD-L1–positive, as defined by having CPS greater than or equal to 1.
At a median follow-up of 10.2 months, the overall response rate for all study participants was 12.2% (12 of 98 patients), which included 3 patients who achieved complete responses and 9 who achieved partial responses. All 12 responses were in patients with PD-L1–positive disease, and when considering only patients with PD-L1–positive tumors, the overall response rate increased to 14.6%.
At 9 or more months of follow-up, 9 of the 12 patients who responded maintained responses, and median duration of response had not yet been reached. Patients with PD-L1–positive tumors had a longer median overall survival than patients with PD-L1–negative tumors (11 months vs 9.4 months).
The incidence of treatment-related adverse events was similar to that of other studies, with 65.3% of patients experiencing an event of any grade and 12.2% experiencing a grade 3 or higher event. Commonly reported adverse events of any grade included hypothyroidism (10.2%), decreased appetite (9.2%), fatigue (9.2%), and diarrhea (8.2%). A total of 4 patients (4.1%) discontinued treatment as a result of adverse events.
Approximately 25% of patients reported immune-mediated adverse events, and 5 of these patients (5.1%) had grade 3 or higher adverse events (2 patients had hepatitis, 2 had severe skin reactions, and 1 had adrenal insufficiency).
Jan Sunde, MD, associate professor and director of the division of gynecologic oncology at Baylor College of Medicine, told Cancer Network that this type of cancer “doesn’t have a good response rate” and that having another treatment option for these women that works “entirely differently” from other standard treatments “is a good thing.”
Ongoing trials are currently evaluating pembrolizumab for patients with advanced cervical cancer in combination with other therapies, including concurrent chemoradiotherapy and sequential chemoradiotherapy (ClinicalTrials.gov identifier: NCT02635360) and chemotherapy and bevacizumab (ClinicalTrials.gov identifier: NCT03367871).