WCLC 2025 - Posters & ePosters-EP.12.04 Efficacy of EGFR TKIs of a Rare but Sensitive Subtype of EGFR L833V/H835L Mutation in Advanced NSCLC

EP.12.04 Efficacy of EGFR TKIs of a Rare but Sensitive Subtype of EGFR L833V/H835L Mutation in Advanced NSCLC

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This study investigates the therapeutic efficacy of EGFR tyrosine kinase inhibitors (EGFR-TKIs) in advanced non-small cell lung cancer (NSCLC) patients harboring rare EGFR mutations L833V and H835L, either alone or in compound forms. These mutations are uncommon compared to prevalent EGFR alterations such as exon 19 deletions and exon 21 L858R mutations, which account for 90% of EGFR mutations and commonly respond well to EGFR-TKIs. Due to their rarity, data on treatment outcomes for L833V/H835L mutations are limited.<br /><br />The authors retrospectively analyzed clinical data from 13 patients diagnosed at Guangdong Lung Cancer Institute between 2016 and 2022 and supplemented this with 13 published cases, compiling a pooled cohort of 26 patients. All patients had adenocarcinoma histology, were mostly non-smokers (18/26), and had a median age of 66 years.<br /><br />Findings showed broad sensitivity of these rare mutations to multiple generations of EGFR-TKIs, including gefitinib, afatinib, osimertinib, and others. Notably, patients with L858R/L833V compound mutations exhibited progression-free survival (PFS) significantly longer than historic data for common EGFR mutations, with some achieving PFS over 70 months. An elderly patient with an isolated H835L mutation had a durable response to afatinib lasting 12.7 months, and other L833V-containing compound mutations also demonstrated superior survival benefits relative to classical EGFR variants.<br /><br />Overall, the study concludes that the L833V/H835L mutations present a rare but highly TKI-sensitive NSCLC subgroup with promising outcomes surpassing those seen in typical EGFR-mutated cases. These results highlight the clinical importance of identifying rare EGFR variants and suggest the need for prospective trials to validate optimal treatment strategies for this population.

Asset Subtitle

Yue-Li Sun

Meta Tag

Speaker Yue-Li Sun

Topic Metastatic Non-small Cell Lung Cancer – Targeted Therapy

Keywords

EGFR tyrosine kinase inhibitors

non-small cell lung cancer

rare EGFR mutations

L833V mutation

H835L mutation

compound EGFR mutations

progression-free survival

adenocarcinoma

targeted therapy

clinical outcomes