2364 - Pembrolizumab vs Chemotherapy in Patients With Advanced/Metastatic Adenocarcinoma (AC) or Squamous Cell Carcinoma (SCC) of the Esophagus as Second-Line Therapy: Analysis of the Chinese Subgroup in KEYNOTE-181

Background

KEYNOTE-181 (NCT02564263) is an open-label, randomized, phase 3 trial of pembrolizumab (P) vs investigator’s choice of single-agent paclitaxel, docetaxel, or irinotecan (standard of care [SOC]) in advanced/metastatic AC or SCC of the esophagus. In the global cohort, P was superior to SOC for OS in pts with PD-L1 combined positive score (CPS) ≥10, with a more favorable safety profile. We present results of the China cohort.

Methods

Eligible pts were randomly assigned 1:1 to receive P 200 mg Q3W for up to 2 y or investigator’s choice of SOC. Randomization was stratified by histology (SCC vs AC) and region (Asia vs rest of world). Primary end points were OS in the intention-to-treat (ITT), SCC, and PD-L1 CPS ≥10 populations.

Results

Of the 123 Chinese pts enrolled, 119 had SCC and 54 had CPS ≥10. Pts were randomly assigned to receive P (62 pts; 60 had SCC; 25 had CPS ≥10) or SOC (61 pts; 59 had SCC; 29 had CPS ≥10). As of Feb 13, 2019, the median follow-up (from randomization, regardless of death) was 15.1 mo (P) vs 14.7 mo (SOC). Median OS was longer with P vs SOC overall (8.4 vs 5.6 mo; HR 0.55; 95% CI 0.36-0.82) and in the SCC (8.4 vs 5.6 mo; HR 0.55; 95% CI 0.37-0.83), and CPS ≥10 groups (12.0 vs 5.3 mo; HR 0.34; 95% CI 0.17-0.69). Median OS for P vs SOC in the CPS <10 group was 6.4 vs 6.1 mo (HR 0.72; 95% 0.43-1.21). OS rates at 12 mo for the P vs SOC groups were 36.3% vs 16.7% overall, 35.7% vs 15.3% in the SCC, and 53.1% vs 16.1% in the CPS ≥10 groups. PFS rates at 6 mo were similar for P vs SOC (26.4% vs 24.1% in the ITT group), but ORR was substantially higher (16.1% vs 3.3% in the ITT group). Median DOR was not reached for P (4.4+ to 14.6+ mo) and was 3.2 mo (2.6-3.9) for the SOC group. Fewer pts receiving P vs SOC had any-grade (76% vs 83%) or grade 3-5 (21% vs 42%) drug-related AEs or drug-related AEs that resulted in discontinuation (6.4% vs 11.9%).

Conclusions

P showed favorable OS, compared with SOC, as second-line therapy for AC/SCC in Chinese pts, with a more favorable safety profile. In China, more patients had SCC than AC and P showed clinically meaningful OS improvement regardless of PD-L1 status. This finding was consistent with that of the Asia group from the full global cohort.

Clinical trial identification

NCT02564263, September 30, 2015.

Editorial acknowledgement

Amy McQuay, PhD, of the ApotheCom pembrolizumab team (Yardley, PA, USA), funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Legal entity responsible for the study

Merck Sharp & Dohme Corp, a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Funding

Merck Sharp & Dohme Corp, a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Disclosure

J. Zhang: Advisory / Consultancy: Bayer; Advisory / Consultancy: BMS; Speaker Bureau / Expert testimony: Roche; Speaker Bureau / Expert testimony: Sanofi; Speaker Bureau / Expert testimony: Merck-Serono; Speaker Bureau / Expert testimony: Pfizer; Speaker Bureau / Expert testimony: Taiho; Speaker Bureau / Expert testimony: HengRui; Speaker Bureau / Expert testimony: Novartis. Y. Cui: Full / Part-time employment: MSD, China. P. Bhagia: Full / Part-time employment: Merck & Co., Inc. S.P. Kang: Full / Part-time employment: Merck & Co., Inc.; Shareholder / Stockholder / Stock options: Celgene; Shareholder / Stockholder / Stock options: Macrogenics; Shareholder / Stockholder / Stock options: Celldex; Shareholder / Stockholder / Stock options: Agenus; Shareholder / Stockholder / Stock options: Pharmacyclics; Shareholder / Stockholder / Stock options: Endocyte. W. Lu: Full / Part-time employment: MSD, China. Y. Zhou: Full / Part-time employment: MSD China. All other authors have declared no conflicts of interest.