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Published in: Gastric Cancer 1/2024

27-10-2023 | Gastric Cancer | Original Article

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

Authors: Jaewon Hyung, Hyungwoo Cho, Hyung-Don Kim, Young Soo Park, Meesun Moon, Min-Hee Ryu, Yoon-Koo Kang

Published in: Gastric Cancer | Issue 1/2024

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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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Metadata
Title
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
Authors
Jaewon Hyung
Hyungwoo Cho
Hyung-Don Kim
Young Soo Park
Meesun Moon
Min-Hee Ryu
Yoon-Koo Kang
Publication date
27-10-2023
Publisher
Springer Nature Singapore
Published in
Gastric Cancer / Issue 1/2024
Print ISSN: 1436-3291
Electronic ISSN: 1436-3305
DOI
https://doi.org/10.1007/s10120-023-01434-w

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