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

摘要

Background In previous studies, the predictive role ofBIMdeletion 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 141EGFR-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. TheBIMgene status was examined by next-generation sequencing. Results The frequency ofBIMdeletion 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% inBIMdeletion group versus 56.4% in wild-typeBIMgroup (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 notBIMdeletion. Conclusions The presence ofBIMdeletion 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 notBIMdeletion.

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