Pembrolizumab for previously treated advanced cervical squamous cell cancer: Preliminary results from the phase 2 KEYNOTE-158 study.

Abstract

5514 Background: In the phase 1b KEYNOTE-028 study, pembrolizumab showed promising activity as monotherapy in patients with advanced cervical cancers that expressed PD-L1. As part of the ongoing, multicohort, phase 2 KEYNOTE-158 study (NCT02628067), we assessed the antitumor activity of pembrolizumab in a larger cohort of patients with previously treated, advanced cervical squamous cell cancer who were enrolled without regard to tumor PD-L1 or other tumor biomarker expression. Methods: Key eligibility criteria for this cohort included age ≥18 years, histologically or cytologically confirmed advanced cervical squamous cell cancer, progression on or intolerance to ≥1 line of standard therapy, ECOG PS 0 or 1, and provision of a tumor sample for biomarker analysis. Patients received pembrolizumab 200 mg Q3W for 2 years or until progression, intolerable toxicity, or physician or patient decision. Clinically stable patients with progression could remain on treatment until progression was confirmed on subsequent assessment. Tumor imaging was performed every 9 weeks for the first 12 months and every 12 weeks thereafter. PD-L1 positivity was evaluated retrospectively by IHC and was defined as a combined positive score ≥1%. Primary end point was ORR assessed per RECIST v1.1 by independent central radiologic review. Planned enrollment is ~100 patients. This efficacy analysis includes patients who had ≥18 weeks of follow-up as of Oct 19, 2016. Results: Among the first 47 patients with advanced cervical cancer who enrolled, ORR was 17% (95% CI, 8%-31%), with 3 confirmed and 5 unconfirmed responses. 41 (87%) patients had PD-L1–positive tumors, and ORR was independent of PD-L1 status. Among the 15 patients who had ≥27 weeks of follow-up, ORR was 27% (95% CI 8%-55%), with 3 confirmed responses and 1 unconfirmed response. Safety and updated efficacy data for 83 patients with ≥27 weeks of follow-up will be available for presentation. Conclusions: Preliminary data from KEYNOTE-158 suggest that pembrolizumab has promising antitumor activity in patients with previously treated advanced cervical squamous cell cancer. The observed ORR with pembrolizumab appears to increase with longer follow-up. Clinical trial information: NCT02628067.