P088 Distribution of Different HER2 Mutations and Their Impact on Clinical Responses to Afatinib in HER2-Mutant Lung Cancer

Abstract

few large-scale studies revealed the clear correlation between age, tumor nodes metastases (TNM) staging and morbidity in this rare population. Method: The age of ALK-positive lung cancer at initial diagnosis were compared between various TNM stages. Clinical characteristics, morbidity and prognosis were analyzed stratified by different age groups. Results: Of 411 patients, the younger group showed more frequent T3/4 stage (P ¼ 0.014), more frequent lymph nodes metastasis (P ¼ 0.011) and more frequent distant metastasis (P ¼ 0.015). Across the entire patient cohort, the median age was 51 years, which decreased steadily with clinical stages (stage I/II vs. III vs. IV, 55 vs. 52 vs. 49 years). There was significant inverse correlation between age and clinical stages (P < 0.001). These laws also existed at various T, N, M categories. What was more, morbidity of ALK rearrangement manifested a steady downward trend with older age groups (40 vs. 40-49 vs. 50-59 vs. 60 years: 18.8% vs. 11.6% vs. 5.0% vs. 2.2%). Surprisingly, ALK-positive patients with stage IIIb-IV disease had much higher incidence than the patients with stage I-IIIa disease (6.1% vs. 3.4%, P < 0.001). Finally, the ALK-positive patients aged younger showed poorer outcomes compared with the older group. Conclusion: TNM staging exhibited a significant inverse correlation with age in ALK-positive lung cancer. More unique therapeutic and research strategies should be required in these patients of young age.

Clinical Characteristics and Outcomes of Non-small Cell Lung Cancer Patients with HER2 Alterations in Korea

“…Even considering the EGFR mutation, the PFS was much longer than the results of previous LUXlung trials [18,19]. Previously, Fang et al [20] showed a divergent therapeutic benefit from afatinib according to mutation type of HER2-altered NSCLC. Patients with G776delinsVC and G778_P780dup derive the greatest benefit from afatinib, while patients with A775_G776insYVMA, co-mutations in the TP53 and PI3K/AKT/mammalian target of rapamycin (mTOR) pathway show primary resistance to afatinib [20].…”

“…Previously, Fang et al [20] showed a divergent therapeutic benefit from afatinib according to mutation type of HER2-altered NSCLC. Patients with G776delinsVC and G778_P780dup derive the greatest benefit from afatinib, while patients with A775_G776insYVMA, co-mutations in the TP53 and PI3K/AKT/mammalian target of rapamycin (mTOR) pathway show primary resistance to afatinib [20]. One preclinical study reported the efficacy of afatinib for NSCLC with HER2 amplification [21].…”