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Pembrolizumab versus chemotherapy as second-line therapy for advanced esophageal cancer: Phase 3 KEYNOTE-181 study.

Abstract

4010
Background: The phase 3 KEYNOTE-181 study compared pembrolizumab (pembro) vs chemo as second-line therapy for patients (pts) with advanced/metastatic squamous cell carcinoma (SCC) and adenocarcinoma (ACC) of the esophagus (NCT02564263). Methods: Eligible pts were randomized 1:1 to pembro 200 mg Q3W for up to 2 years or choice of paclitaxel, docetaxel, or irinotecan. Randomization was stratified by histology (SCC vs adenocarcinoma) and region (Asia vs rest of world). Primary end points were OS in the SCC, PD-L1 combined positive score (CPS) ≥10, and the ITT. Secondary endpoints included PFS, ORR, safety; exploratory endpoints included health-related quality of life (HRQoL) in CPS ≥10. Results: 628 pts were randomized (401 with SCC; 222 with CPS ≥10). As of Oct. 15, 2018, median follow-up was 7.1 mo (pembro) vs 6.9 mo (chemo). In CPS ≥10, OS was superior with pembro vs chemo (median 9.3 vs 6.7 mo; HR 0.69; 95% CI 0.52-0.93; P= 0.0074). In CPS ≥10 SCC, median OS was 10.3 mo vs 6.7 mo and in CPS ≥10 ACC, median OS was 6.3 mo vs 6.9 mo; 12-mo OS rates were higher with pembro vs chemo (Table). In SCC, median OS was 8.2 mo vs 7.1 mo; HR 0.78; 95% CI 0.63-0.96; P= 0.0095. In the ITT, median OS was 7.1 mo vs 7.1 mo; HR 0.89; 95% CI 0.75-1.05; P= 0.0560. Updated OS will be presented. Grade 3-5 drug-related AEs (≥10% incidence in either arm) included decreased white blood cells (0% vs 10%), decreased neutrophils (0.3% vs 10%). In CPS ≥10, HRQoL improved with pembro vs chemo only for EQ-5D VAS (difference in LS mean change from baseline 5.57; 95% CI 0.58-10.56). Conclusions: Pembro significantly improved OS vs chemo as second-line therapy for advanced esophageal cancer with PD-L1 CPS ≥10, with a more favorable safety profile and stable and similar QOL. These data support pembro as a new second-line standard of care for esophageal cancer with PD-L1 CPS ≥10. Clinical trial information: NCT02564263.
 CPS ≥10
TotalSCCACC
 Pembro
N = 107
Chemo
N = 115
Pembro
N = 85
Chemo
N = 82
Pembro
N = 22
Chemo
N = 33
12-mo OS, %432048232315
Median PFS (95% CI), mo2.63.03.22.32.13.7
 (2.1-4.1)(2.1-3.7)(2.1-4.4)(2.1-3.4)(1.9-3.5)(2.0-5.7)
12-mo PFS, %217237147
ORR, %21.56.1227183
Median DOR (range), mo9.37.79.37.7Not reached4.4
 (2.1+ to 22.6+)(4.3 to 16.8+)(2.1+ to 18.8+)(4.3 to 16.8+)(6.5 to 22.6+)(4.4-4.4)

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Journal of Clinical Oncology
Pages: 4010

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Published in print: May 20, 2019
Published online: May 26, 2019

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Manish A. Shah
Weill Cornell Medicine, New York-Presbyterian Hospital, New York, NY;
Antoine Adenis
Institut du Cancer de Montpellier, Montpellier, France;
Peter C. Enzinger
Dana-Farber Cancer Institute, Boston, MA;
Takashi Kojima
National Cancer Center Hospital East, Kashiwa, Japan;
Kei Muro
Aichi Cancer Center Hospital, Nagoya, Japan;
Jaafar Bennouna
Institut de Cancérologie de l'Ouest, Nantes, France;
Eric Francois
Department of Medical Oncology, Centre Antoine-Lacassagne, Nice, France;
Chih-Hung Hsu
National Taiwan University Hospital, Taipei, Taiwan;
Toshikazu Moriwaki
University of Tsukuba, Tsukuba, Japan;
Sung-Bae Kim
University of Ulsan College of Medicine, Seoul, South Korea;
Se-Hoon Lee
Division of Hematology and Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea;
Ken Kato
Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan;
Lin Shen
Beijing Cancer Hospital, Beijing, China;
Shukui Qin
PLA Cancer Center of Bayi Hospital Affiliated to Nanjing University of Chinese Medicine, Nanjing, China;
Paula Ferreira
Instituto Português de Oncologia Porto, Porto, Portugal;
Ruixue Wang
MSD China, Beijing, China;
Pooja Bhagia
Merck & Co., Inc., Kenilworth, NJ;
S. Peter Kang
Merck & Co., Inc., Kenilworth, NJ;
Jean-Philippe Metges
Centre Hospitalier Regional Universitaire (CHRU) de Brest–Hopital Morvan, Brest, France;
Toshihiko Doi
National Cancer Center Hospital East, Kashiwa, Japan;
Weill Cornell Medicine, New York-Presbyterian Hospital, New York, NY; Institut du Cancer de Montpellier, Montpellier, France; Dana-Farber Cancer Institute, Boston, MA; National Cancer Center Hospital East, Kashiwa, Japan; Aichi Cancer Center Hospital, Nagoya, Japan; Institut de Cancérologie de l'Ouest, Nantes, France; Department of Medical Oncology, Centre Antoine-Lacassagne, Nice, France; National Taiwan University Hospital, Taipei, Taiwan; University of Tsukuba, Tsukuba, Japan; University of Ulsan College of Medicine, Seoul, South Korea; Division of Hematology and Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea; Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan; Beijing Cancer Hospital, Beijing, China; PLA Cancer Center of Bayi Hospital Affiliated to Nanjing University of Chinese Medicine, Nanjing, China; Instituto Português de Oncologia Porto, Porto, Portugal; MSD China, Beijing, China; Merck & Co., Inc., Kenilworth, NJ; Centre Hospitalier Regional Universitaire (CHRU) de Brest–Hopital Morvan, Brest, France

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Manish A. Shah, Antoine Adenis, Peter C. Enzinger, Takashi Kojima, Kei Muro, Jaafar Bennouna, Eric Francois, Chih-Hung Hsu, Toshikazu Moriwaki, Sung-Bae Kim, Se-Hoon Lee, Ken Kato, Lin Shen, Shukui Qin, Paula Ferreira, Ruixue Wang, Pooja Bhagia, S. Peter Kang, Jean-Philippe Metges, Toshihiko Doi
Journal of Clinical Oncology 2019 37:15_suppl, 4010-4010

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