Oncologic equivalence of brand-name vs generic imatinib in neoadjuvant <i>KIT</i> exon 11 GIST: A real-world international cohort study.

Abstract

11535 Background: Neoadjuvant imatinib is routinely used to facilitate resection of localized gastrointestinal stromal tumors (GIST) with KIT exon 11 mutations. However, whether generic formulations achieve oncologic outcomes equivalent to the brand-name drug in curative-intent neoadjuvant therapy remains unknown. Methods: We performed a retrospective, international dual-institution cohort study of 131 patients with localized KIT exon 11–mutant GIST treated with neoadjuvant imatinib followed by surgical resection (2010–2025) at UC San Diego and Fondazione IRCCS Istituto Nazionale dei Tumori (Milan). Patients received either brand-name or generic imatinib based on institutional practice. The primary endpoint was tumor size reduction. Secondary endpoints included histopathologic response and overall survival. Multivariable regression and Kaplan–Meier analyses were performed. Results: Of 131 patients, 71 (54%) received brand-name and 60 (46%) received generic imatinib. Objective response (≥30% tumor reduction) occurred in 54% vs 37%, respectively (P=0.078). Median tumor size reduction was −33.3% with brand-name and −25.5% with generic imatinib (P=0.105). In multivariable analysis, longer neoadjuvant duration was independently associated with greater tumor reduction (β=−0.02 per day; 95% CI, −0.04 to −0.00; P=0.04), whereas imatinib formulation, dose, and treatment center were not. Pathologic outcomes, including viable tumor percentage (P=0.053), necrosis (P=0.777), and mitotic index (P=0.889), were similar between groups. Five-year overall survival was 87.2% with no difference by formulation (log-rank P=0.24). Conclusions: In this first international analysis of neoadjuvant therapy for KIT exon 11–mutant GIST, generic imatinib demonstrated oncologic equivalence to the brand-name formulation across tumor response, pathologic, and survival outcomes. As generic imatinib use has expanded globally following patent expiration, these findings reinforce its role as a clinically effective, cost-efficient, and accessible therapy. Demonstrating therapeutic equivalence in the neoadjuvant setting has direct implications for practice guidelines, formulary decisions, and equitable delivery of precision oncology worldwide. Tumor size reduction and objective response by imatinib formulation. Outcome Brand-name (n=71) Generic (n=60) P Value ≥30% tumor size reduction 38 (53.5%) 22 (36.7%) 0.078 Any tumor size reduction 59 (83.1%) 49 (81.7%) 1.0 ≥20% tumor size increase 5 (7.0%) 2 (3.3%) 0.452 Tumor size reduction, (median [IQR]) −33.3% (−45 to −18.4) −25.5% (−38.8 to −10.5) 0.11 Note: P values calculated using Fisher’s exact test for categorical outcomes and Mann–Whitney U test for continuous variables. Tumor size reduction reported as median (interquartile range, IQR).