ArticleTranslational lung cancer research2025
Efficacy and safety of first-generation epidermal growth factor receptor tyrosine kinase inhibitors in retreatment of patients without T790M.
Article in Translational lung cancer research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03382795 (Retreatment With 1st Generation EGFR TKIs in Sensitizing EGFR Mutation Positive Non-Squamous Cell Carcinoma Patients Who Previously Treated With EGFR TKI and Cytotoxic Chemotherapy), which is not on this map. Not yet cited in PubMed.
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Retreatment With 1st Generation EGFR TKIs in Sensitizing EGFR Mutation Positive Non-Squamous Cell Carcinoma Patients Who Previously Treated With EGFR TKI and Cytotoxic Chemotherapy
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11 authors.
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Abstract
Background: Patients receiving first-line epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) and undergoing second and/or third-line cytotoxic chemotherapy may experience regrowth of EGFR (+) clones. Retreatment with EGFR TKIs can provide antitumor effects and potentially induce T790M-positive conversion. This study evaluated the efficacy, safety, and T790M (+) conversion rates in patients without T790M mutation at the second biopsy retreated with first-generation EGFR TKIs as third-line or subsequent therapy. Methods: This open-label, multi-center, prospective phase II trial (NCT03382795) enrolled patients with non-small cell lung cancer (NSCLC) previously treated with first- or second-generation EGFR TKIs and cytotoxic chemotherapy They were retreated with gefitinib or erlotinib. Key endpoints included objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety. Results: Among 63 patients (34 on gefitinib, 29 on erlotinib), ORR was 14.3%. Median PFS was 2.2 months, and median OS was 8.6 months. Adverse events occurred in 82.5% of patients, primarily grade ≤2. The T790M conversion rate was 31.7% and was significantly associated with prior EGFR TKI exposure duration (P=0.047). Patients with T790M conversion had a median OS of 29.3 months, significantly (P<0.001) longer than the median OS of 6.0 months for non-converters. Next-generation sequencing (NGS) of pre-retreatment blood samples identified additional T790M mutations (20.8%) undetected by conventional testing. Low TP53 expression showed a non-significant trend toward higher tendency T790M conversion (66.7% Conclusions: EGFR retreatment induced T790M conversion in 32% of cases, enabling third-generation EGFR TKIs, leading to a substantial improvement in median OS. Blood-based NGS identified additional T790M mutations, undetected by routine polymerase chain reaction (PCR). EGFR TKI retreatment with blood-based NGS may enhance patient prognosis by identifying additional T790M positive mutations.
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