Assessing Graded Histological Regression as Basis for Treatment Modification after Neoadjuvant Therapy in LAGC: An Exploratory Phase II Study.

Abstract

Background: Whether to change adjuvant regimen after ineffective neoadjuvant chemotherapy in locally advanced gastric cancer (LAGC) remains unclear. We conducted an exploratory study on whether graded histologic regression (GHR) < 50% was a potential indicator for regimen modification.

Patients and methods: The study was a prospective, single-center, open-label, randomized, phase II trial. Patients were randomly assigned to group A (paclitaxel-modified regimen) and group B (original regimen) for adjuvant chemotherapy. The primary endpoint was disease-free survival (DFS), with secondary endpoints of overall survival (OS) and safety.

Results: Between May 2017 and August 2025, 58 patients with postoperative GHR < 50% were enrolled and randomly allocated to group A (n = 28) or group B (n = 30). After a median of 19.3 months follow-up, group A had longer median DFS (25.2 months versus 11.4 months) (hazard ratio [HR] 0.4711, 95% confidence interval [CI] 0.2501-0.8874; P = 0.020) and median OS (32.0 months versus 18.0 months) (HR 0.5088, 95% CI 0.2667-0.9708; P = 0.040) than group B. Regimen modification was identified as independent prognostic factor for DFS and OS. In subgroup analysis, compared with ypN0-2, patients with ypN3 stage (P = 0.047) were more likely to experience OS benefits by regimen modification. Patients with ypTNM III stage (P = 0.046) had more DFS benefits from regimen alteration than ypTNM I-II. Regarding adverse events, except higher nausea incidence, chemotherapy change did not significantly increase other adverse reactions.

Conclusions: GHR < 50% may indicate the need to adjust adjuvant chemotherapy regimen in LAGC. A larger study is needed to validate its final survival impact.