22P Evaluation of co-mutation in EGFR-mutant non-small cell lung cancer by next generation sequencing (NGS): Retrospective cohort study in South Korea

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are standard First-line treatments for advanced non-small cell lung cancer (NSCLC) harboring EGFR mutations. However, despite optimal therapies, not all patients have a positive response. The existence of simultaneous mutations may contribute to resistance. The objective of this study was to evaluate the effect of simultaneous mutations on the prognosis of patients receiving first-line EGFR TKI treatment for EGFR-mutated NSCLC. This was a single center, retrospective cohort study that included patients aged 19 or older with EGFR-mutant advanced NSCLC using Next Generation Sequencing (NGS). Participants were treated with first-line EGFR-TKIs. The primary endpoint was time-to-treatment discontinuation (TTD). 254 patients were enrolled in the study from January 2017 to December 2022. Median age was 62.5 (range 37-75), and 44.5% (113/254) was males. The most common tumor type was Adenocarcinoma (250/254, 98.42%). Among Co-mutation, the most common mutation was TP53(157/254, 61.8%). The overall median TTD of this cohort was 17 months. There were differences in median TTD between EGFR mutation without TP53 and EGFR mutation with TP53 (25 vs 16 months, P value= 0.032) (Table). Baseline characteristics of study population and time-to-treatment discontinuation (TTD) of 1st line EGFR TKI in EGFR-mutant NSCLC by Next Generation Sequencing.Table: 22PEGFR mutation without TP53 (n=97)EGFR mutation with TP53 (n=157)All patients (n=254)Median age (range)68(54-75)61.9(37-75)62.5 (37-75)Sex, Male, n (%)48(49.48)65(41.4)113 (44.5)EGFR mutation,n(%)L858R19delOthers38(39.18)56(57.73)3(6.09)67(42.68)75(47.77)15(9.55)105 (41.33)130 (51.18)18(7.08)Co-mutation,n,(%)METCNVPIK3CARB1NOTCHNF12(2.06)2(2.06)5(5.15)2(2.06)4(4.12)1(1.03)2(1.27)2(1.27)10(6.37)21(13.38)3(1.91)2(1.27)4(1.57)4(1.57)15(5.90)23(9.06)7(2.75)3(1.18)mTTD,months(95%CI)25(15.7-34.3)16(13.0-19.0)17(13.9-20.0) Open table in a new tab Advanced EGFR mutant NSCLC patients with TP53 had a shorter time-to-treatment discontinuation(TTD) compared to those with EGFR mutation. Further investigations are needed for prognostic and response evaluations with other identified mutations.