Nintedanib in advanced solid tumors: A meta-analysis of randomized controlled trials.

Abstract

e15170 Background: Nintedanib (Vargatef/BIBF 1120) is an anti-angiogenic tyrosine kinase inhibitor evaluated across multiple advanced solid tumors, yet its overall efficacy and safety profile in randomized settings remain uncertain. Methods: We performed a PRISMA 2020 compliant systematic review and meta-analysis (PROSPERO-registered), searching PubMed, Scopus, Embase, Cochrane Library, and ClinicalTrials.gov from inception for phase II/III RCTs in adults with advanced/recurrent/metastatic solid tumors comparing nintedanib-based therapy vs placebo or other anticancer regimens. We pooled HRs for time-to-event outcomes and RRs for dichotomous outcomes using fixed/random-effects models based on I², conducted tumor-type subgroup analyses for PFS/OS, and assessed risk of bias using RoB 2. Results: Eighteen RCTs comprising 7,542 participants were included. Overall, nintedanib was associated with a borderline improvement in PFS versus control (HR 0.86, 95% CI 0.74–1.00; I² = 73.2%), with a clearer benefit in thoracic cancers (HR 0.79, 95% CI 0.73–0.87) and no significant PFS advantage in gynecologic, gastrointestinal, or urological subgroups. OS was not significantly improved (HR 0.92, 95% CI 0.84–1.01; I² = 42.3%), although thoracic cancers showed a subgroup signal (HR 0.84, 95% CI 0.73–0.96). ORR did not differ between groups (RR 1.00, 95% CI 0.79–1.27; I² = 22.5%). Grade ≥3 adverse events were not significantly increased overall (RR 1.14, 95% CI 0.90–1.43), but treatment discontinuation was higher with nintedanib (RR 1.53, 95% CI 1.18–1.98). Nintedanib increased risks of gastrointestinal (notably diarrhea) and hepatic toxicities (ALT/AST elevations), with additional signals for fatigue, leukopenia, and sepsis. Conclusions: Across randomized trials in advanced solid tumors, nintedanib demonstrates a modest and tumor type–dependent improvement in disease control, with the most consistent signal in thoracic malignancies, but without a reproducible benefit in overall survival or objective response. Its clinical utility may be limited by tolerability, particularly gastrointestinal and hepatotoxic adverse events, and higher discontinuation rates.