Re-evaluating the neutropenia-survival paradigm in irinotecan-based therapy for advanced gastric cancer: post-hoc analysis of the RINDBeRG trial

Background: Chemotherapy-induced neutropenia (CIN) has been considered a favorable prognostic marker across multiple cytotoxic regimens for gastrointestinal malignancies. However, its prognostic relevance in irinotecan (IRI)-based therapy for advanced gastric cancer (AGC) remains unclear. Methods: This post-hoc analysis used data from the phase III RINDBeRG trial comparing ramucirumab (RAM) plus IRI with IRI monotherapy as third- or later-line treatment for RAM-refractory AGC. Overall survival (OS) was evaluated according to the occurrence of grade 3 or higher neutropenia, defined as CIN. OS was also evaluated according to the baseline absolute neutrophil count (ANC), stratified by quartile-based cutoffs. Results: Among the 393 patients in the safety population, 44.5% and 28.5% in the RAM + IRI and IRI arms developed CIN, respectively. Baseline characteristics were generally comparable, with some imbalances across baseline ANC groups. In the RAM + IRI arm, those with and without CIN had a median OS of 9.7 and 8.9 months, respectively (HR = 0.84; 95% CI, 0.62–1.13; p = 0.25). In the IRI arm, those with and without CIN had a median OS of 8.4 and 8.6 months, respectively (HR = 0.85; 95% CI, 0.60–1.19; p = 0.34). Higher baseline ANC was associated with shorter OS, particularly in the RAM + IRI arm (7.3 vs. 10.9 months; HR = 1.83; 95% CI 1.14–2.94; p = 0.01). Conclusions: Unlike other cytotoxic regimens, CIN was not associated with survival in AGC patients receiving IRI with or without RAM. The clinical relevance of baseline ANC warrants further investigation. Trial registration: jRCT2031200106.