Concomitant genetic alterations having greater impact on the clinical benefit of EGFR-TKIs in EGFR-mutant advanced NSCLC than BIM deletion polymorphism.

ABSTRACT

BACKGROUND: In previous studies, the predictive role of BIM deletion polymorphism with respect to responses to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) has been controversial. The potential reasons for these inconsistent findings were unknown. METHODS: Data from CTONG0901 clinical trial and medical records of Guangdong Lung Cancer Institute (GLCI) were retrospectively pooled. A total of 194 and 141 EGFR-mutant non-small cell lung cancer (NSCLC) patients treated with first- and second-generation EGFR-TKIs were examined in the CTONG0901 and GLCI cohorts, respectively. Sixty-eight patients were treated with third-generation EGFR-TKIs in the GLCI cohort. The BIM gene status was examined by next-generation sequencing. RESULTS: The frequency of BIM deletion polymorphism was 11.3% and 17.0% in CTONG0901 and GLCI cohorts, respectively. For first- and second-generation EGFR-TKIs in CTONG0901 cohort, objective response (ORR) was 54.5% in BIM deletion group versus 56.4% in wild-type BIM group (P = .87); disease control rate (DCR) was 90.9% versus 88.4% (P = 1.00); progression-free survival (PFS) was 10.5 versus 11.2 months (P = .59); and overall survival (OS) was 20.5 versus 20.5 months (P = .73). In GLCI cohort, ORR was 54.2% versus 60.7% (P = .55); DCR was 91.7% versus 96.6% (P = .27); PFS was 10.1 versus 11.6 months (P = .63); and OS was 58.5 versus 45.0 months (P = .93). For third-generation EGFR-TKIs, ORR was 18.2% versus 63.2% (P = .02); DCR was 81.8% versus 96.5%, (P = .12); PFS was 5.8 versus 9.0 months (P = .13); and OS was 30.0 versus 24.8 months (P = .85). Cox regression analysis showed that concomitant genetic alterations could adversely affect the response to EGFR-TKIs, but not BIM deletion. CONCLUSIONS: The presence of BIM deletion showed no relation to an impaired response to first-, second-, and third-generation EGFR-TKIs in NSCLC patients. The factors influencing the response of EGFR-TKIs were concomitant genetic alterations, but not BIM deletion.