Lazertinib versus Platinum-Based Chemotherapy with Epidermal Growth Factor Receptor (EGFR)-Positive Non-Small-Cell Lung Cancer after Failing EGFR-Tyrosine Kinase Inhibitor: A Real-World External Comparator Study.

Simple Summary: Lazertinib, a third-generation EGFR-TKI, selectively inhibits both the common EGFR mutation and the T790M mutation in NSCLC patients. No previous studies have compared lazertinib with platinum-based chemotherapy. In this external control retrospective study, we have compared the efficacy of lazertinib and platinum-based chemotherapy in patients who had previously received EGFR-TKI treatment. This study included 200 patients from the LASER 201, LASER 301, and LASER-PMS studies, and 334 patients who received platinum-based chemotherapy after prior EGFR-TKI treatment for SMC. After propensity score matching, we selected 156 patients from each group. The PFS was significantly longer in those patients treated with lazertinib than in those treated with platinum-based chemotherapy (10.97 months vs. 5.10 months) after PSM. Lazertinib also demonstrated superior OS, ORR, and TTD compared to platinum-based chemotherapy. Based on this retrospective, external control study, lazertinib demonstrated significantly superior efficacy compared to platinum-based chemotherapy. The external controls provide important context to evaluate efficacy in single-arm studies. Background: Lazertinib is a third-generation tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR-TKI) that selectively inhibit common EGFR mutation and T790M mutation in non-small-cell lung cancer (NSCLC) patients. No previous studies have compared lazertinib to platinum-based chemotherapy. We have compared lazertinib with platinum-based chemotherapy in EGFR-mutated NSCLC patients after previous EGFR-TKI therapy. Methods: We retrospectively compared 200 patients from LASER201, LASER301, and LASER-PMS studies to 334 patients who were treated with platinum-based chemotherapy after previous EGFR-TKI from the Samsung Medical Center. After propensity score matching (PSM), we selected 156 patients from each group. The primary outcome was progression-free survival (PFS), with overall survival (OS), objective response rate (ORR), and time to treatment discontinuation (TTD) as secondary outcomes. Results: The median follow-up of PFS was 15.61 months in the lazertinib group and 21.67 months in the external control group. The PFS was significantly longer in patients who were treated with lazertinib than those treated with platinum-based chemotherapy (10.97 months vs. 5.10 months; adjusted hazard ratio (HR) 0.40; 95% confidence interval (CI), 0.29–0.55; p < 0.01) after PSM. Lazertinib showed superior OS (32.23 months vs. 18.73 months; adjusted HR 0.45; 95% CI, 0.29–0.69; p < 0.001), ORR (64.1% vs. 47.4%), and TTD (11.66 months vs. 6.73 months; adjusted HR 0.54; 95% CI, 0.39–0.75; p < 0.001) compared to platinum-based chemotherapy. Conclusion: Based on this retrospective, external control study, lazertinib has demonstrated significantly better efficacy compared with platinum-based chemotherapy. The external controls provide important context to evaluate efficacy in single-arm studies. [ABSTRACT FROM AUTHOR]