Do Generic EGFR-TKIs Perform as Well as Innovators? Real-World Evidence from Gefitinib-Treated EGFR-Mutated NSCLC in...

Gefitinib is standard first-line therapy for $EGFR$-mutated non-small cell lung cancer (NSCLC). Following Indonesia's 2020 transition to generic gefitinib in national procurement, real-world comparative data remain limited. This study compared clinical outcomes between innovator and generic gefitinib in Indonesian referral hospitals.

We conducted a retrospective cohort study of adults with EGFR-mutated NSCLC receiving first-line innovator or generic gefitinib between 2019-2022 at national cancer center and national respiratory center. The effectiveness was evaluated using progression-free survival (PFS) estimated by Kaplan-Meier and compared with the log-rank test; hazard ratios (HRs) were derived from Cox regression. Adverse events (AEs) were abstracted from patients' medical records based on physicians' documentation in the clinical progress notes and analyzed using Mann-Whitney tests. Multivariable analyses were performed to evaluate the association between gefitinib type (generic vs. innovator) and clinical outcomes while adjusting for potential confounders, including demographics, smoking status, comorbidities, disease stage, ECOG performance status, radiotherapy history, COVID-19 history, mutation subtype, and hospital. The follow-up period was 18 months within a 4-year horizon.

A total of 192 patients met the inclusion criteria (innovator n = 124; generic n = 68). The median PFS was 12.2 months (95% CI, 8.7-15.7) in the innovator group and 16.4 months (95% CI, 13.7-19.1) in the generic group. Although the generic formulation demonstrated a numerically longer median PFS, the difference was not statistically significant (HR = 1.61, 95% CI, 0.98-2.63; p = 0.104). Multivariate analysis showed that no baseline variable was significantly associated with PFS after adjustment. Safety profiles were generally comparable, but dermatologic and gastrointestinal AEs occurred more frequently with the generic formulation, with significantly higher frequencies (rate-adjusted) of diarrhoea, paronychia, and stomatitis (p = 0.002, 0.011, and 0.001, respectively). Other AEs, including dyspepsia, alopecia, neuropathy, and AST/ALT elevation did not differ significantly between groups.

The generic formulation demonstrated comparable efficacy to the innovator drug in terms of progression-free survival, although a higher incidence of certain mild-to-moderate adverse events was noted. These findings support the therapeutic use of the generic gefitinib with careful monitoring of tolerability.