T cell-inflamed gene expression profile and PD-L1 expression and pembrolizumab efficacy in advanced esophageal cancer

Manish A Shah; Takashi Kojima; Daniel Hochhauser; Peter Enzinger; Judith Raimbourg; Antoine Hollebecque; Florian Lordick; Sung-Bae Kim; Masahiro Tajika; Albert Craig Lockhart; Hendrick-Tobias Arkenau; Farid El-Hajbi; Mukul Gupta; Per Pfeiffer; Pooja Bhagia; Zhu Alexander Cao; Jared Lunceford; Shailaja Suryawanshi; Mark Ayers; Matthew J Marton; Ken Kato

doi:10.2217/fon-2021-1134

T cell-inflamed gene expression profile and PD-L1 expression and pembrolizumab efficacy in advanced esophageal cancer

Future Oncol. 2022 Jul 19. doi: 10.2217/fon-2021-1134. Online ahead of print.

Authors

Manish A Shah¹, Takashi Kojima², Daniel Hochhauser³, Peter Enzinger⁴, Judith Raimbourg⁵, Antoine Hollebecque⁶, Florian Lordick⁷, Sung-Bae Kim⁸, Masahiro Tajika⁹, Albert Craig Lockhart¹⁰, Hendrick-Tobias Arkenau¹¹, Farid El-Hajbi¹², Mukul Gupta¹³, Per Pfeiffer¹⁴, Pooja Bhagia¹⁵, Zhu Alexander Cao¹⁵, Jared Lunceford¹⁵, Shailaja Suryawanshi¹⁵, Mark Ayers¹⁵, Matthew J Marton¹⁵, Ken Kato¹⁶

Affiliations

¹ Weill Cornell Medicine/New York-Presbyterian Hospital, New York, NY 10065, USA.
² National Cancer Center Hospital East, Kashiwa, Japan.
³ University College London Hospitals NHS Foundation Trust, London, UK.
⁴ Dana-Farber Cancer Institute, Boston, MA 02215, USA.
⁵ Institut de Cancérologie de l'Ouest, St Herblain, Nantes, France.
⁶ Département de Médecine Oncologique, Gustave Roussy, Villejuif, France.
⁷ Department of Medicine II, University Cancer Center Leipzig, Leipzig University Medical Center, Leipzig, Germany.
⁸ Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
⁹ Department of Endoscopy, Aichi Cancer Center Hospital, Nagoya, Japan.
¹⁰ University of Miami Miller School of Medicine, Miami, FL 33136, USA.
¹¹ Sarah Cannon Research Institute, University College, London, UK.
¹² Service d'Hépato Gastro-Entérologie et de Cancérologie Digestive, Centre Oscar-Lambret, Lille, France.
¹³ Sansum Clinic, Santa Barbara, CA 93110, USA.
¹⁴ Department of Oncology, Odense University Hospital, Odense, Denmark.
¹⁵ Merck & Co., Inc., Rahway, NJ 07033, USA.
¹⁶ Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan.

PMID: 35852104
DOI: 10.2217/fon-2021-1134

Abstract

Aim: Investigate the relationship between response to pembrolizumab and expression of the 18-gene T cell-inflamed gene expression profile (Tcell_infGEP) or PD-L1 combined positive score (CPS) in esophageal cancer. Materials & methods: This analysis included heavily pretreated patients with advanced/metastatic esophageal/gastroesophageal junction adenocarcinoma or squamous cell carcinoma who received pembrolizumab in the single-arm, phase II study KEYNOTE-180. PD-L1 CPS was evaluated with PD-L1 IHC 22C3 pharmDx. Results: In patients with squamous cell carcinoma, trends toward enrichment for responders were observed for patients with PD-L1 CPS ≥10 tumors. In patients with adenocarcinoma, a trend was observed for Tcell_infGEP but not for PD-L1. Conclusion: Tcell_infGEP and PD-L1 CPS may enrich for responders to pembrolizumab in patients with esophageal cancer. Clinical trial registration: NCT02559687 (ClinicalTrials.gov).

Keywords: esophageal cancer; gene expression profile; pembrolizumab; programmed death ligand 1; tumor microenvironment.

Associated data

ClinicalTrials.gov/NCT02559687

Grants and funding

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