Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea;
Jaewon Hyung , Young Soo Park , Hyungwoo Cho , Hyung-Don Kim , Min-Hee Ryu , Yoon-Koo Kang
Background: Benefit of perioperative or postoperative chemotherapy for resectable locally advanced gastric cancer (LAGC) with DNA mismatch repair (MMR) deficiency is controversial due to concerns about the potential detrimental effect of perioperative chemotherapy. In this sub-analysis of the phase 3 PRODIGY trial, we evaluated the association between the MMR status and outcomes of resectable LAGC treated with perioperative or postoperative chemotherapy. Methods: Among 249 patients with resectable LAGC enrolled in the PRODIGY trial treated with either perioperative chemotherapy (preoperative docetaxel, oxaliplatin, and S-1 [DOS] followed by surgery and postoperative S-1; CSC arm) or surgery and postoperative S-1 (SC arm) at Asan Medical Center, those in the full analysis set with available tissue for MMR status assessment by immunohistochemistry were included in this study. Progression-free survival (PFS) was compared according to the MMR status and treatment arm. In the CSC arm, the pathologic complete response (pCR) rate was compared according to the MMR status. Results: A total of 231 patients (CSC arm, n = 108; SC arm, n = 123) were included in the study (median age, 58 years [range, 27–75]). Twenty-one patients (CSC arm, n = 8 [7.4%]; SC arm, n = 13 [10.6%]) had deficient MMR (D-MMR) tumors while the rest had proficient MMR (P-MMR) tumors. There was no significant difference in the baseline characteristics including the clinical stage according to the MMR status. Among patients with P-MMR tumors, PFS tended to be superior in the CSC arm than in the SC arm (hazard ratio [HR] 0.67 [95% confidence interval (CI) 0.44–1.03]; log-rank P = 0.07). Among patients with D-MMR tumors, the PFS of the CSC arm was not inferior to that of the SC arm (HR 0.50 [95% CI 0.10–2.60]; log-rank P = 0.41). In the CSC arm, the pCR rate was 5.0% (5/100) and 12.5% (1/8) in patients with P-MMR and D-MMR tumors, respectively. Conclusions: In this sub-analysis of the PRODIGY trial, the PFS of the CSC arm was not inferior to that of the SC arm among patients with D-MMR LAGC. Among patients who received preoperative DOS, the pCR rate was not lower in patients with D-MMR tumors compared with those with P-MMR tumors. Perioperative chemotherapy consisting of preoperative DOS followed by surgery and postoperative S-1 may be recommended for patients with LAGC regardless of the MMR status.
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Abstract Disclosures
2023 ASCO Annual Meeting
First Author: Yoon-Koo Kang
2023 ASCO Gastrointestinal Cancers Symposium
First Author: Hyung-Don Kim
2024 ASCO Gastrointestinal Cancers Symposium
First Author: Anant Ramaswamy
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