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

Abstract

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