Efficacy of First Line Afatinib in Epidermal Growth Factor Receptor Mutation Positive Metastatic Non-squamous Non-small Cell Lung Cancer: A Prospective Cohort Single-arm Observational Study among Indian Patients

Introduction: Lung cancer remains a leading health burden in India, with Non-Small Cell Lung Cancer (NSCLC) being the most prevalent type. Epidermal Growth Factor Receptor (EGFR) mutations, commonly seen in non-smokers, offer an opportunity for targeted therapy. afatinib, a second-generation EGFR TKI, has shown improved outcomes over first-generation TKIs, but Indian data remains scarce. Aim: To evaluate the safety and efficacy of first-line afatinib in Indian patients with metastatic EGFR mutation-positive NonSquamous NSCLC (NS-NSCLC). Materials and Methods: The present prospective, single-arm observational study was conducted from June 2016 to May 2018 at Dharamshila Narayana Superspeciality Hospital, New Delhi, India. Adults with Stage IV, EGFR mutation-positive NSNSCLC were treated with oral afatinib (starting dose 40 mg/ day). Responses were assessed every 12 weeks via Positron Emission Tomography-Computed Tomography (PET-CT) scan using Positron Emission Response Criteria in Solid Tumours (PERCIST) criteria. Patients progressing on treatment were evaluated for T790M mutation and switched to Osimertinib if found positive for mutation. Data were analysed using Statistical Package for Social Sciences (SPSS) version 21.0. Categorical variables were expressed as percentages, and continuous variables as mean±SD or median values. Survival outcomes were estimated using Kaplan-Meier analysis, with comparisons by log-rank test. A p-value <0.05 was considered statistically significant. Results: Of the 217 patients screened, 27 were enrolled in the study. The median age was 55 years. Among them, 17 patients (62.96%) were female and 19 (70.37%) were never-smokers. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-1 was observed in 20 patients (74.07%). The most common EGFR mutation was exon 19 deletion, present in 15 patients (55.56%). The median Progression-Free Survival (PFS) was 13.8 months, and 18 patients (66.67%) achieved one-year Overall Survival (OS). The Objective Response Rate (ORR) was 77.78% (n=21), with 25 patients (92.59%) achieving clinical benefit. The most common adverse events were diarrhoea in 21 patients (77.78%) and rash/acne in 20 patients (74.07%), though severe toxicities were uncommon. Dose reduction was required in 9 patients (33.33%), without any observed impact on PFS. Conclusion: First-line afatinib was found to be effective and well tolerated in Indian patients with EGFR mutation-positive metastatic NS-NSCLC. It provided superior PFS compared with other first-generation TKIs like gefitinib and erlotinib, and with manageable adverse effects. afatinib also resulted in meaningful improvements in response rate, OS, and clinical benefit. These results support afatinib as a standard first-line treatment option in this patient population.