Pembrolizumab treatment of advanced cervical cancer: updated results from the phase II KEYNOTE-158 study

Objectives: Pembrolizumab (pembro) showed durable antitumor activity and manageable safety in patients (pts) with advanced cervical cancer in an earlier interim analysis of KEYNOTE-158 (NCT02628067). Based on those results, the US FDA granted accelerated approval of pembro for pts with advanced, PD-L1-positive cervical cancer that progressed on or after chemotherapy. We present an updated analysis of pts included in the cervical cancer cohort of KEYNOTE-158 based on 17 months of additional follow-up. Methods: KEYNOTE-158 is a phase 2 basket study investigating the antitumor activity of pembro across several cancer types. Key eligibility criteria for the cervical cancer cohort included histologically or cytologically confirmed disease, progression on or intolerance to ≥1 line of standard therapy, an ECOG PS of 0 or 1, and provision of a tumor sample for biomarker analysis. Pts received pembro 200 mg once every 3 weeks for 2 years or until progression, intolerable toxicity, or physician or patient decision. Tumor imaging was performed every 9 weeks for the first 12 months, and every 12 weeks thereafter. PD-L1 positivity, defined as a combined positive score (CPS) ≥1, was evaluated retrospectively by immunohistochemistry. The primary endpoint was the objective response rate (ORR) assessed per RECIST v1.1 by independent central radiology review. Secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. Results: A total of 98 pts were treated. Median age was 46 (range, 24 to 75) years, 65.3% had ECOG PS 1, and 94.9% had stage M1 disease. A total of 83.7% of enrolled pts had PD-L1–positive tumors. As of the June 27, 2019 data cutoff, the median follow-up duration, defined as first dose of study medication to data cutoff, was 36.9 (range, 34.3 to 41.0) months. In the updated analysis, 2 partial responses (PR) converted to complete responses (CR) and 2 additional PR occurred for a total of 5 CR and 9 PR; ORR was 14.3% (95% CI, 8.0% to 22.8%). A total of16 pts had stable disease (SD), and the disease control rate (CR+PR+SD) was 30.6%. All 14 responses were in pts with PD-L1–positive tumors, resulting in an ORR of 17.1% (95% CI, 9.7% to 27.0%) in the PD-L1–positive cohort (N=82) and 0.0% (95% CI, 0.0% to 21.8%) in the PD-L1–negative cohort. A total of 7 of 14 responses were ongoing after ≥24 months of follow-up. Median DOR had not been reached (range, 3.7+ to 35.2+). Median (95% CI) PFS and OS were 2.1 (2.1 to 2.2) months and 9.3 (7.6 to 11.7) months, respectively. Treatment-related adverse events (AEs) occurred in 65.3% of pts, and the most common were hypothyroidism (11.2%), fatigue (11.2%), and decreased appetite (9.2%). 12.2% of pts had treatment-related grade 3-4 AEs; there were no grade 5 AEs. Conclusions: With 17 months of additional follow-up, pembro continues to show durable antitumor activity and manageable safety in pts with advanced cervical cancer, similar to the previous report. Pembrolizumab (pembro) showed durable antitumor activity and manageable safety in patients (pts) with advanced cervical cancer in an earlier interim analysis of KEYNOTE-158 (NCT02628067). Based on those results, the US FDA granted accelerated approval of pembro for pts with advanced, PD-L1-positive cervical cancer that progressed on or after chemotherapy. We present an updated analysis of pts included in the cervical cancer cohort of KEYNOTE-158 based on 17 months of additional follow-up. KEYNOTE-158 is a phase 2 basket study investigating the antitumor activity of pembro across several cancer types. Key eligibility criteria for the cervical cancer cohort included histologically or cytologically confirmed disease, progression on or intolerance to ≥1 line of standard therapy, an ECOG PS of 0 or 1, and provision of a tumor sample for biomarker analysis. Pts received pembro 200 mg once every 3 weeks for 2 years or until progression, intolerable toxicity, or physician or patient decision. Tumor imaging was performed every 9 weeks for the first 12 months, and every 12 weeks thereafter. PD-L1 positivity, defined as a combined positive score (CPS) ≥1, was evaluated retrospectively by immunohistochemistry. The primary endpoint was the objective response rate (ORR) assessed per RECIST v1.1 by independent central radiology review. Secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. A total of 98 pts were treated. Median age was 46 (range, 24 to 75) years, 65.3% had ECOG PS 1, and 94.9% had stage M1 disease. A total of 83.7% of enrolled pts had PD-L1–positive tumors. As of the June 27, 2019 data cutoff, the median follow-up duration, defined as first dose of study medication to data cutoff, was 36.9 (range, 34.3 to 41.0) months. In the updated analysis, 2 partial responses (PR) converted to complete responses (CR) and 2 additional PR occurred for a total of 5 CR and 9 PR; ORR was 14.3% (95% CI, 8.0% to 22.8%). A total of16 pts had stable disease (SD), and the disease control rate (CR+PR+SD) was 30.6%. All 14 responses were in pts with PD-L1–positive tumors, resulting in an ORR of 17.1% (95% CI, 9.7% to 27.0%) in the PD-L1–positive cohort (N=82) and 0.0% (95% CI, 0.0% to 21.8%) in the PD-L1–negative cohort. A total of 7 of 14 responses were ongoing after ≥24 months of follow-up. Median DOR had not been reached (range, 3.7+ to 35.2+). Median (95% CI) PFS and OS were 2.1 (2.1 to 2.2) months and 9.3 (7.6 to 11.7) months, respectively. Treatment-related adverse events (AEs) occurred in 65.3% of pts, and the most common were hypothyroidism (11.2%), fatigue (11.2%), and decreased appetite (9.2%). 12.2% of pts had treatment-related grade 3-4 AEs; there were no grade 5 AEs. With 17 months of additional follow-up, pembro continues to show durable antitumor activity and manageable safety in pts with advanced cervical cancer, similar to the previous report.