Efficacy and safety of irinotecan-based therapy in elderly patients with advanced gastric cancer receiving third-line or later chemotherapy: post-hoc age-subgroup analysis of the rindberg trial.

[BACKGROUND] In late-line treatment for advanced gastric cancer (AGC), evidence supporting the use of irinotecan in older patients remains limited. We conducted a post-hoc age-subgroup analysis of the phase III RINDBeRG study, which randomized AGC patients previously treated with ramucirumab-based chemotherapy to receive ramucirumab plus irinotecan (RAM + IRI) or irinotecan alone (IRI).

[METHODS] Patients were classified as elderly (≥ 70 years; n = 83 [RAM + IRI], 80 [IRI]) or non-elderly (< 70 years; n = 117, 113). Efficacy outcomes-including overall survival (OS), progression-free survival (PFS), and overall response rate (ORR)-and safety were compared. Prognostic factors for OS were explored via multivariable Cox regression.

[RESULTS] OS and PFS did not differ significantly between age groups. In the RAM + IRI group, median OS was 9.7 vs. 8.9 months (hazard ratio [HR] 0.85, 95% confidence interval [CI] 0.63-1.15), and PFS was 4.0 vs. 3.6 months (HR 0.84, CI 0.63-1.12). In the IRI group, OS was 8.5 months in both groups (HR 0.99, CI 0.7-1.34), and PFS was 3.1 vs. 2.2 months (HR 0.87, CI 0.65-1.17). ORRs were 20.5% vs. 14.5% (RAM + IRI) and 18.8% vs. 9.7% (IRI) in elderly vs. non-elderly patients. Grade ≥ 3 adverse events were comparable. Multivariable analysis identified ECOG PS 1, peritoneal metastasis, elevated LDH, modified Glasgow Prognostic Score ≥ 1, and low alkaline phosphatase as poor prognostic factors. Age was not prognostic.

[CONCLUSIONS] Irinotecan-based therapy offers comparable efficacy and tolerability in older and younger patients with refractory AGC.