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261 Association of T-cell–inflamed gene expression profile and PD-L1 status with efficacy of pembrolizumab in patients with esophageal cancer from KEYNOTE-180
  1. Manish Shah1,
  2. Takashi Kojima2,
  3. Daniel Hochhauser3,
  4. Peter Enzinger4,
  5. Judith Raimbourg5,
  6. Antoine Hollebecque6,
  7. Florian Lordick7,
  8. Sung-Bae Kim8,
  9. Masahiro Tajika9,
  10. Heung Tae Kim10,
  11. A Craig Lockhart11,
  12. Hendrick-Tobias Arkenau12,
  13. Farid El-Hajbi13,
  14. Per Pfeiffer14,
  15. Pooja Bhagia15,
  16. Z Alexander Cao15,
  17. Jared Lunceford15,
  18. Shailaja Suryawanshi15,
  19. Mark Ayers15,
  20. Matt Marton15 and
  21. Ken Kato16
  1. 1Weill Cornell Medical College, New York, NY, USA
  2. 2National Cancer Center Hospital East, Chiba, Japan
  3. 3University College London Hospitals, London, UK
  4. 4Dana-Farber Cancer Institute, Boston, MA, USA
  5. 5Institut de Cancérologie de l’Ouest, St Herblain, France
  6. 6Institut Gustave Roussy, Villejuif, France
  7. 7University Cancer Center Leipzig, Leipzig, Germany
  8. 8Asan Medical Center, Seoul, Korea, Republic of
  9. 9Aichi Cancer Center Hospital, Aichi, Japan
  10. 10National Cancer Center, Goyang, Korea, Republic of
  11. 11University of Miami, Miami, FL, USA
  12. 12Sarah Cannon Research Institute, London, UK
  13. 13Centre Oscar-Lambret, Lille, France
  14. 14Odense University Hospital, Odense, Denmark
  15. 15Merck and Co., Inc., Kenilworth, NJ, USA
  16. 16National Cancer Center Hospital, Tokyo, Japan


Background Key biomarkers under investigation for the ability to predict response to monotherapy PD-1 inhibitors such as pembrolizumab include PD-L1, TMB, MSI, and T-cell–inflamed gene expression profile (GEP). The KEYNOTE-180 trial (NCT02559687) was a single-arm phase 2 study of pembrolizumab as third-line or greater therapy in advanced/metastatic esophageal/gastroesophageal junction adenocarcinoma or squamous cell carcinoma (SCC). ORR was 9.9% and median DOR was NR at the primary analysis. We investigated the relationship in KEYNOTE-180 between response to pembrolizumab and T-cell–inflamed GEP or PD-L1 expression by histology.

Methods Patients received pembrolizumab 200 mg Q3W for ≤2 years until disease progression, toxicity, or withdrawal. The end points for this analysis were ORR, DOR, and PFS per RECIST v1.1 by central review and OS in the SCC and adenocarcinoma populations by GEP (non-low [≥–1.540] or low [<–1.540]; cutoff prespecified) and PD-L1 (CPS ≥10 or <10). Tumor GEP was determined using the NanoString nCounter Analysis System. PD-L1 expression was characterized using PD-L1 IHC 22C3 pharmDx. Data cutoff date was July 30, 2018.

Results Of 121 total patients, 118 had an evaluable GEP score and 121 had an evaluable PD-L1 CPS. Fifty-one patients (42.1%) had GEPnon-lowtumors, 58 (48.0%) had CPS ≥10 tumors, and 31 (25.6%) had GEPnon-low/CPS ≥10 tumors; 63 patients (52.1%) had SCC and 58 (47.9%) had adenocarcinoma. ORR was 15.4% with GEPnon-low and 13.5% with GEPlow among patients with SCC and 12% and 0% among patients with adenocarcinoma, respectively (table 1). ORR was 20% with CPS ≥10 and 7.1% with CPS <10 among patients with SCC and 4.3% and 5.7%, respectively, among patients with adenocarcinoma (table 2). Median OS was slightly higher among patients with SCC in the GEPnon-low subgroup and the CPS ≥10 subgroup versus GEPlow and CPS <10 subgroups, respectively (tables 1, 2); this trend was reversed among patients with adenocarcinoma (tables 1, 2). Median PFS ranged from 1.9 to 2.1 across histology/biomarker subgroups. Median DOR was NR regardless of GEP or CPS status (tables 1, 2).

Abstract 261 Table 1

Response by GEP status and histologyaAnalysis by biomarker status was not possible because of the small sample size.

Abstract 261 Table 2

Response by PD-L1 status and histologyaAnalysis by biomarker status was not possible because of the small sample size.

Conclusions In KEYNOTE-180, data in a small number of patients suggested that measures of inflammation, like PD-L1 and GEP, may enrich for responses to pembrolizumab. In SCC, some trends toward enrichment were observed for both biomarkers, although the trend was stronger for PD-L1 CPS ≥10. In adenocarcinoma, a trend was observed for GEP but not for PD-L1; the small number of responders is limiting, and further studies are needed to understand molecular correlates in adenocarcinoma.

Acknowledgements Medical writing and/or editorial assistance was provided by Tim Peoples, MA, ELS, and Holly C. Cappelli, PhD, CMPP, of the ApotheCom pembrolizumab team (Yardley, PA, USA). This assistance was funded by Merck Sharp & Dohme Corp, a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Trial Registration ClinicalTrials. gov, NCT02559687

Ethics Approval The study and the protocol were approved by the institutional review board or ethics committee at each site.

Consent All patients provided written informed consent to participate in the clinical trial.

This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See:

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