Combination chemotherapy with gefitinib as first-line treatment in EGFR-mutated metastatic non-small cell lung cancer: A retrospective Indian experience

ABSTRACT Background: Metastatic non-small cell lung cancer (NSCLC) harboring targetable epidermal growth factor receptor ( EGFR ) mutations is primarily treated with osimertinib. However, limited access to osimertinib in resource-constrained settings necessitates exploration of alternative treatment options. Objectives: Our primary objective was to assess progression-free survival (PFS) following first-line combination therapy with gefitinib and chemotherapy in EGFR -mutated metastatic NSCLC. Secondary objectives included evaluating the objective response rate (ORR) and treatment-related toxicities. Materials and Methods: This retrospective analysis included 12 Indian patients with EGFR mutations (exon 19 deletion or exon 21 L858R) treated from January 2019 to March 2023 with first-line gefitinib and pemetrexed-carboplatin chemotherapy. Imaging (CT/PET-CT) was done at baseline, post chemotherapy, and every three months thereafter. Liquid biopsies for acquired T790M mutation were performed at progression. Results: Among 12 patients, eight had exon 19 deletions, and four had exon 21 L858R mutations. Patients received a median of four chemotherapy cycles, with maintenance gefitinib alone ( n = 6) or combined with pemetrexed ( n = 5). ORR was 75% (2 complete, 7 partial responses), and DCR was 91.6%. Median PFS was 11 months (95% CI: 8.9-13.0); 2-year OS rate was 85.7%. Common toxicities included grade 1-2 skin rash ( n = 10, 83.3%) and diarrhea ( n = 4, 33.3%). Limitations were a small sample size and variability in second-line therapy availability. Conclusion: Gefitinib combined with chemotherapy demonstrated meaningful clinical efficacy and manageable toxicity as first-line treatment in EGFR -mutated metastatic NSCLC, providing a valuable alternative in settings where osimertinib is inaccessible.