Real-world analysis of survival outcomes in advanced EGFR-mutant NSCLC patients treated with platinum-pemetrexed after EGFR-TKI treatment failure.

Introduction: EGFR tyrosine kinase inhibitors (TKIs) are the standard therapy for non-small-cell lung cancer (NSCLC) patients with EGFR-activating mutations in the first-line setting. Despite initial efficacy, resistance to EGFR-TKIs often develops, and platinum-based chemotherapy is the predominant subsequent treatment. For this study, we aimed to identify prognostic factors for overall survival (OS) and progression-free survival (PFS) among advanced EGFR-mutant NSCLC patients receiving platinum-pemetrexed after progression on EGFR-TKIs. Our analysis specifically focuses on 1st-line treatments limited to 1st- or 2nd-generation EGFR-TKIs, while not restricting later-line treatments involving osimertinib prior to chemotherapy.
Materials and Methods: From 2012 to 2017, 363 patients who received first-line treatment with first- or second-generation EGFR-TKIs, including gefitinib, erlotinib, and afatinib were enrolled. Some patients received different EGFR-TKIs, including osimertinib, as later-line treatment before platinum-pemetrexed.
Results: Median OS from the initiation of platinum-pemetrexed was 22.0 months and median PFS with platinum-pemetrexed was 6.2 months. In the multivariate Cox model, we identified three independent prognostic factors for better OS: postoperative recurrence (HR: 0.34, p = 0.004), first-line EGFR-TKI PFS ≥12 months (HR: 0.54, p = 0.002), and osimertinib treatment after platinum-pemetrexed (HR: 0.56, p = 0.005) while BMI <18.5 indicated poor prognosis (HR:1.76, p = 0.049). No statistically significant independent prognostic factors for PFS were found. Receiving osimertinib before platinum-pemetrexed treatment did not impact PFS with platinum-pemetrexed treatment (HR: 1.11, p = 0.64).
Conclusion: Postoperative recurrence, first-line EGFR-TKI PFS ≥12 months and osimertinib treatment after platinum-pemetrexed predicted better OS, while BMI <18.5 predicted worse OS. Osimertinib treatment before platinum-pemetrexed treatment did not affect the efficacy of platinum-pemetrexed.
Competing Interests: Declaration of competing interest Dr. Yao reports personal fees from AstraZeneca, Boehringer Ingelheim, and Pfizer, outside the submitted work. Dr. Liao reports personal fees from AstraZeneca, Roche, Boehringer Ingelheim, Eli Lilly, Pfizer, MSD Oncology, Novartis, Bristol-Myers Squibb, and Chugai Pharma Taiwan, outside the submitted work. Dr. Ho reports personal fees from Boehringer Ingelheim, Eli Lilly, Amgen, Roche/Genentech/Chugai, MSD, and Pfizer, outside the submitted work; Dr. Shih reports grants from Taipei City Thoracic Disease Academic Research and Education Foundation and personal fees from ACTgenomics, Amgen, Genconn Biotech, AstraZeneca, Roche, Bayer, Boehringer Ingelheim, Eli Lilly, Pfizer, Novartis, Merck Sharp & Dohme, Chugai Pharma, Takeda, CStone Pharmaceuticals, Janssen, TTY Biopharm, Orient EuroPharma, MundiPharma, Ono Pharmaceutical, and Bristol-Myers Squibb, outside the submitted work. Dr. Chen reports personal fees from AstraZeneca, Roche, Novartis, Pfizer, Eli Lilly, Merck Sharp and Dohme, Ono Pharmaceutical, and Boehringer Ingelheim, outside the submitted work. Dr. Yang reports personal fees and other from Amgen, grants, personal fees and other from AstraZeneca, personal fees and other from Bayer, personal fees and other from Boehringer Ingelheim, personal fees and other from Bristol Myers Squibb, personal fees and other from Daiichi Sankyo, other from Eli Lilly, personal fees and other from Merck KGaA, Darmstadt, Germany, personal fees and other from Merck Sharp & Dohme, personal fees and other from Novartis, personal fees from Ono Pharmaceuticals, personal fees from Pfizer, personal fees and other from Roche/Genentech, personal fees and other from Takeda Oncology, personal fees and other from Yuhan Pharmaceuticals, other from JNJ, other from Puma Technology, other from Gilead, other from GSK, outside the submitted work. The other authors declare no conflict of interest.
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