The efficacy of molecule-matched treatment on hyperprogressive disease after immunotherapy: A retrospective study from the Molecular Tumor Board registry.

Abstract

e15187 Background: Hyperprogressive disease (HPD) is a severe adverse event following immunotherapy, often resulting in rapid patient deterioration and death. The treatment options for HPD are limited. Certain genetic alterations are believed to be associated with the onset of HPD. This study aims to evaluate the efficacy of molecular tumor board (MTB)-guided molecule-matched treatment (MT) in managing HPD. Methods: This retrospective study included 40 confirmed HPD patients enrolled in the MTB registry at the Department of Oncology, Second Hospital of Tianjin Medical University, between January 2018 and January 2024. The patients were categorized based on the initial treatment: the MT high-level evidence group (MTH), which included lung cancer with EGFR mutations, and urothelial carcinoma with FGFR mutations or ERBB2 overexpression (n = 6); the MT low-level evidence group (MTL), which included FGF/FGFR aberrations, RAS/RAS-STK11 alterations, TP53 mutations, and PAM signaling pathway dysregulation (n = 17); the non-MT treatment group (NMT, n = 7); and the limited/no treatment group (LNT, n = 10). Clinical information, overall survival (OS), and cumulative progression-free survival (cPFS) were collected. Kaplan-Meier survival analysis and Cox regression models were used to assess the efficacy of the different treatment groups for HPD. Results: Median OS was significantly longer in the MTL and MTH groups compared to the LNT group (3.32 months), with values of 9.47 months and 15.12 months, respectively. Pairwise analysis revealed a significantly longer median OS in the MTL group compared to the LNT group (HR = 0.04, 95% CI: 0.01-0.19). No significant difference was found between the MTL and MTH groups (0.41, 0.15-1.15). Significant differences in median cPFS (mcPFS) were observed only between the NMT and MTH groups ( P = 0.04), with an mcPFS of 2.87 months in the NMT group and 9.43 months in the MTH group. No significant difference in mcPFS was found between the NMT and MTL groups or between the MTL and MTH groups. MT showed clinical benefit (defined as a PFS ratio ≥ 1.3) in 87.0% of patients, and 66.7% of patients exhibited an improvement in ECOG PS from ≥ 2. Conclusions: MTB-guided MT, utilizing actionable targets and potentially targetable molecular alterations, significantly improved survival outcomes for HPD patients. These results support the feasibility and efficacy of MT in managing HPD and lay the foundation for future large-scale clinical trials.