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DNA mismatch repair deficiency and outcomes of patients with locally advanced gastric cancer treated with preoperative docetaxel, oxaliplatin, and S-1 plus surgery and postoperative S-1 or surgery plus postoperative S-1: a sub-analysis of the phase 3 PRODIGY trial

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Abstract

Background

The benefit of adjuvant chemotherapy for locally advanced gastric cancer (LAGC) patients with DNA mismatch repair (MMR) deficiency (D-MMR) is controversial due to concerns about its potential detrimental effect. The PRODIGY trial showed the survival benefit of adding preoperative docetaxel, oxaliplatin, and S-1 (DOS) to surgery plus postoperative S-1 for LAGC patients. In this sub-analysis, we evaluated the benefit of preoperative DOS according to MMR status.

Methods

Among patients enrolled in the PRODIGY trial treated with either preoperative DOS followed by surgery and postoperative S-1 (CSC arm), or surgery and postoperative S-1 (SC arm) at Asan Medical Center (n = 249), those in the full analysis set with available tissue to assess MMR status were included in the present analysis.

Results

A total of 231 patients (CSC arm, n = 108; SC arm, n = 123) were included (median age, 58 years [range, 27–75]), and 21 patients (CSC arm, n = 8 [7.4%]; SC arm, n = 13 [10.6%]) had D-MMR tumors. Progression-free survival and overall survival tended to be superior in the CSC arm than in the SC arm among D-MMR patients (HR 0.48 [95% CI 0.09–2.50]; log-rank P = 0.37 and HR 0.55 [95% CI 0.11–2.86]; log-rank P = 0.46, respectively), as well as among proficient MMR (P-MMR) patients (HR 0.68 [95% CI 0.46–1.03]; log-rank P = 0.07 and HR 0.75 [95% CI 0.49–1.14]; log-rank P = 0.17, respectively).

Conclusion

Preoperative DOS followed by surgery and postoperative S-1 may be considered a treatment option for LAGC patients regardless of MMR status.

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Acknowledgements

The data analyzed were from the PRODIGY study, which was sponsored by Sanofi.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or no-for-profit sectors.

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Author notes

  1. Jaewon Hyung, Hyungwoo Cho, and Hyung-Don Kim contributed equally as co-first authors.

Authors and Affiliations

  1. Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-Ro 43-Gil, Songpa-Gu, Seoul, 05505, Republic of Korea

    Jaewon Hyung, Hyungwoo Cho, Hyung-Don Kim, Meesun Moon, Min-Hee Ryu & Yoon-Koo Kang

  2. Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea

    Young Soo Park

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Contributions

Conceptualization: YKK. Data acquisition and collection: HWC, YSP, MSM, MHR, and YKK. Data analysis: J Hyung, HWC, HDK, MHR, and YKK. Manuscript drafting: J Hyung, HDK, and YKK. Review and editing of the manuscript: All authors.

Corresponding author

Correspondence to Yoon-Koo Kang.

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Conflict of Interest

Conflicts of interest Nothing directly related to this work. Out of this work, YK Kang has served as a consultant for Liscure, ALX Oncology, Zymeworks, Amgen, Novartis, Macrogenics, Daehwa, Blueprint, Surface Oncology, BMS, and Merck (MSD). MH Ryu received an honorarium and served on the advisory boards of Ono Pharmaceutical, BMS, MSD, Lily, Taiho, Novartis, Daiichi Sankyo, and AstraZeneca, and served as a consultant for DAEHWA Pharmaceutical, BMS, Lily, and Ono Pharmaceutical.

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Hyung, J., Cho, H., Kim, HD. et al. DNA mismatch repair deficiency and outcomes of patients with locally advanced gastric cancer treated with preoperative docetaxel, oxaliplatin, and S-1 plus surgery and postoperative S-1 or surgery plus postoperative S-1: a sub-analysis of the phase 3 PRODIGY trial. Gastric Cancer 27, 110–117 (2024). https://doi.org/10.1007/s10120-023-01434-w

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