Abstract 2364
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.
Resources from the same session
3668 - Patient Demographics and Management Landscape of Metastatic Colorectal Cancer in the Third Line Setting: real-world data in an Australian Population
Presenter: Sandy Tun Min
Session: Poster Display session 2
Resources:
Abstract
3907 - Exploration of efficacious alternative regorafenib regimens to manage hand-foot-skin-reaction (HFSR)
Presenter: Axel Grothey
Session: Poster Display session 2
Resources:
Abstract
3958 - Quality of Life (QoL) in Metastatic Colorectal Cancer (mCRC) in the Real World: Final Results of a European Survey
Presenter: Zorana Maravic
Session: Poster Display session 2
Resources:
Abstract
3563 - BISQUIT: A Randomized Phase II Study of the Administration of Prebiotics and Probiotics During Definitive Treatment With Chemotherapy-radiotherapy for Patients With Squamous Cell Carcinoma of the Anal Canal
Presenter: Rachel Riechelmann
Session: Poster Display session 2
Resources:
Abstract
1184 - iSCORE: Immunotherapy Sequencing in COlon and REctal Cancer
Presenter: Fiona Turkes
Session: Poster Display session 2
Resources:
Abstract
3346 - Phase II study of preoperative (PREOP) chemoradiotherapy (CTRT) plus avelumab (AVE) in patients (PTS) with locally advanced rectal cancer (LARC): The AVANA Study
Presenter: Lisa Salvatore
Session: Poster Display session 2
Resources:
Abstract
3895 - A phase II study of capecitabine plus concomitant radiation therapy followed by durvalumab (MEDI4736) as preoperative treatment in rectal cancer: PANDORA study.
Presenter: Maria Aurelia Barbera
Session: Poster Display session 2
Resources:
Abstract
2012 - Open Label Phase III Study of Arfolitixorin vs. Leucovorin in mFOLFOX-6 for First Line Treatment of Metastatic Colorectal Cancer: AGENT
Presenter: Josep Tabernero
Session: Poster Display session 2
Resources:
Abstract
2198 - SOLSTICE, a phase 3, randomized, open label study of trifluridine/tipiracil+bevacizumab (bev) versus capecitabine+bev for the 1L treatment of patients with unresectable metastatic colorectal cancer (mCRC) who are not candidates for intensive therapy
Presenter: Thierry Andre
Session: Poster Display session 2
Resources:
Abstract
2921 - A Phase Ib/ II Trial to Assess the Safety and Efficacy of CXD101 in Combination with the PD-1 Inhibitor Nivolumab in Patients with Metastatic, Previously-Treated, Microsatellite-Stable (MSS) Colorectal Carcinoma (short title CAROSELL)
Presenter: Mark Saunders
Session: Poster Display session 2
Resources:
Abstract