1414P - Impact of co-mutations on the prognosis of targeted therapy in EGFR-mutant advanced NSCLC: A result of real-world study

Background

The aim of this study was to observe the concurrent genetic profiles of EGFR-mutated advanced Chinese non-small cell lung cancer (NSCLC), as well as to analyze the effects of diverse concurrent genetic alterations on the prognosis in EGFR-mutated NSCLC treated in first-line with EGFR-TKI.

Methods

The CAPTRA-Lung (NCT03334864) database was used to retrieve 307 patients with advanced EGFR-mutated NSCLC between January 1, 2018 and January 1, 2022 in our institution. Of those, 103 patients were detected by next-generation sequencing (NGS) and the results showed other concurrent genetic alterations. We divided them into two cohorts: those who were sequenced with NGS at baseline were included in cohort 1, and those who received NGS after progression to first-line therapy were contained in cohort 2. The follow-up deadline was October 1, 2022.

Results

The following genes are found to be most frequent in the entire cohort: TP53 mutation (n = 64, 62.14%), EGFR amplification (n = 14, 13.59%), KRAS mutation (n = 13, 12.62%), PIK3CA mutation (n = 13, 12.62%), and DNMT3A mutation (n = 13, 12.62%). Most of the TP53 mutations have been identified in exons 5 (16/64), 6 (9/64), 7 (10/64), 8(9/64), etc. For KRAS mutations, G12V (4/13) and G12S (3/13) were the most common mutation types, and E545K (5/13) and H1047R (2/13) were the most frequently alterations observed in PIK3CA. Cohort 1 constituted 68 patients (mean [SD] age, 60.93 [9.051] years; 55.9% female). Multivariate analysis demonstrated that alterations in TP53 (HR 1.946, 95% CI 1.112-3.403; P = 0.020) and MET (HR 3.581, 95% CI 1.070-11.992; P = 0.039) were independently correlated to poor progression-free survival (PFS). Cohort 2 encompassed 35 patients (mean [SD] age, 56.80 [8.741] years; 71.4% female). Multifactorial analysis showed that TP53 mutation (HR 2.198, 95% CI 1.006-4.803; P = 0.048) and RB1 mutation (HR 8.798, 95% CI 1.604-48.269; P = 0.012) were independent risk factors for PFS with first-line targeted therapy.

Conclusions

This research added to the evidence that co-alterations such as TP53, MET, and RB1 are prospective prognostic biomarkers in NSCLC patients treated with EGFR-TKI.

Clinical trial identification

NCT03334864.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.