Pembrolizumab in previously treated metastatic esophageal cancer: Longer term follow-up from the phase 2 KEYNOTE-180 Study.

Abstract

4032 Background: In the phase 2, open-label, KEYNOTE-180 (NCT02559687) study, after a median follow-up of 5.8 months, pembrolizumab (pembro) provided antitumor activity with durable responses in pts with previously treated, advanced/metastatic adenocarcinoma (EAC) including Siewert type 1 adenocarcinoma of the gastroesophageal junction or squamous cell carcinoma (ESCC) of the esophagus. Here we present results of an additional 10 months of follow-up. Methods: Eligible pts with metastatic esophageal cancer, ≥2 prior lines of therapy, and tumor samples evaluable for biomarker expression, received pembro 200 mg Q3W for up to 2 years, or until disease progression, unacceptable toxicity, or withdrawal. Tumor response was assessed Q9W (RECISTv1.1, central review). PD-L1+ pts had combined positive score ≥10 using IHC (22C3 antibody). Primary endpoint was objective response rate (ORR). Secondary endpoints included safety, DOR, PFS, and OS. Results: Of 121 pts enrolled, 63 (52%) had ESCC and 58 (48%) had PD-L1+ (combined positive score ≥10) tumors. As of July 30, 2018, median follow-up duration, from randomization to data cutoff, was 5.8 mo (range, 0.2 mo to 27.8+ mo). ORR (CR+PR) was 10% (95% CI, 5%-17%); 2 (2%) CR,10 (8%) PR, 25 (21%) SD. Median DOR was not reached ([NR] range, 2.1 mo to 25.1+ mo). Median PFS was 2 mo (95% CI, 1.9%-2.1%) with 9-mo PFS rate of 9%. Median OS was 5.8 mo (4.5-7.2) with 12 mo OS rate of 27%. In ESCC, ORR was 14% (95% CI, 7%-25%); 2 (3%) CR, 7 (11%) PR, with median DOR NR (range, 4.2 mo to 25.1+ mo). In EAC, ORR was 5% (95% CI, 1-14); 3 PR, with median DOR NR (range, 2.1 mo to 15.6+ mo). In PD-L1+ pts, ORR was 14% (95% CI, 6%-25%); 1 (2%) CR, 7 (12%) PR with median DOR NR (range, 4.2 mo to 25.1+ mo). In PD-L1- pts ORR was 6% (95% CI, 2%-16%); 1 (2%) CR, 3 (5%) PR; median DOR NR (range, 2.1 mo to 17.3+ mo). Overall, 19 (16%) pts had treatment-related grade 3-5 AEs. Seven (6%) pts discontinued due to a treatment-related AE. There was one treatment-related death from pneumonitis. Conclusions: Pembro continued to provide durable clinical benefit with a manageable safety profile for pts with heavily pretreated esophageal cancer, with conversions of PR to CR observed. Clinical trial information: NCT02559687.