Tyrosine Kinase Inhibitor versus Physician Choice Chemotherapy in Second-Line Epidermal Growth Factor Receptor Mutation Non-Small Cell Lung Cancer: Post hoc Analysis of Randomized Control Trial

Abstract Background: There is a paucity of prospective data for patients who progressed after first-line tyrosine kinase inhibitor (TKI) or pemetrexed doublet among epidermal growth factor receptor (EGFR) mutation-positive metastatic non-small cell lung cancer (NSCLC). Aim: The aim of the study was to evaluate the outcome of second-line therapy in patients who progressed on TKI or pemetrexed doublet in EGFR mutation-positive NSCLC. Objective: The objective of the study was to calculate response rates, progression-free survival (PFS), and overall survival (OS) of patients receiving second-line therapy in EGFR mutation NSCLC. Materials and Methods: Post hoc analysis of second-line therapy among patients enrolled in randomized control trial comparing TKI versus pemetrexed doublet in EGFR mutation NSCLC. Kaplan–Meir statistics were used for PFS and OS. Impact of variables was measured with Log-rank test. Results: One hundred and eighty-seven patients who progressed on first-line therapy and received second-line agents were analyzed. Male:female: 110 (56.3%):77 (41.2%). One hundred and thirteen patients received gefitinib, while 74 received chemotherapy. Response rate (complete response + partial response) was 53% versus 24% in gefitinib versus chemotherapy group (RECIST v1.1). PFS was 7.4 months versus 4.4 months (P = 0.001), while OS was 14 months versus 9.7 months (P = 0.007), in gefitinib versus chemotherapy group, respectively. Response to TKI significantly improves PFS (10.8 months vs. 3.9 months, P = 0.001) and OS (21.4 months vs. 8.9 months, P = 0.03). Rash, pruritus, dry skin, fatigue, diarrhea, and paronychia were common toxicities of TKI. Conclusion: Second-line TKI improves outcome in EGFR mutation-positive NSCLC who progressed after first-line chemotherapy. Response to therapy, whether with TKI or chemotherapy, favorably impacts outcomes.