Pembrolizumab treatment of advanced cervical cancer: Updated results from the phase 2 KEYNOTE-158 study.

Abstract

5522 Background: The KEYNOTE-158 study (NCT02628067) is a phase II basket study investigating the antitumor activity of pembrolizumab, an IgG4 anti-PD-1 monoclonal antibody, in 11 cancer types. An updated analysis of all 98 patients (pts) included in the cervical cancer cohort is presented. Methods: Key eligibility criteria for this cohort included histologically or cytologically confirmed advanced cervical 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. Pts received pembrolizumab 200 mg Q3W for 2 y or until progression, intolerable toxicity, or physician or patient decision. Tumor imaging was performed every 9 wks for the first 12 mo, and every 12 wks thereafter. PD-L1 positivity, defined as a combined positive score (CPS) ≥1, was evaluated retrospectively by IHC. Primary endpoint was ORR assessed per RECIST v1.1 by independent central radiology review. Secondary endpoints included DOR, PFS, OS, and safety. Results: 98 pts were treated. Median age was 46.0 (range, 24-75) y, 65.3% had ECOG PS 1, and 93.9% had stage M1 disease. 83% of enrolled pts had PD-L1+ tumors. As of the August 23, 2017 data cutoff, the median follow-up duration was 10.3 mo (range, 0.6 to 18.0 mo). ORR was 13.3% (95% CI, 7.3%-21.6%), with 3 CR and 10 PR. 17 pts had SD, and the DCR was 30.6%. All 13 responses were in pts with PD-L1+ tumors, and the ORR was 16.0% (95% CI, 8.8%-25.9%) in the PD-L1-positive cohort (N = 81). 9 of 13 responses were ongoing after ≥9 mo follow-up. Median DOR had not been reached (range, 3.7+ to 12.4+). Median (95% CI) PFS and OS were 2.1 mo (2.0-2.2 mo) and 9.4 mo (7.9-13.4 mo), respectively. Treatment-related AEs occurred in 65.3% of pts, and the most common were hypothyroidism (10.2%), decreased appetite (9.2%), fatigue (9.2%), and diarrhea (8.2%). 11.2% of pts had treatment-related grade 3-4 AEs. Conclusions: Similar to the initial report, durable antitumor activity and manageable safety were demonstrated with pembrolizumab in advanced cervical cancer. Clinical trial information: NCT02628067.