Customized first-line chemotherapy according to ERCC1 and RRM1 SNPs in advanced NSCLC patients: A phase II study.

Abstract

e18074 Background: Excision repair cross complementing group 1 (ERCC1) and ribonucleotide reductase1 (RRM1) expression levels are predictive of CT efficacy in some malignancies. “Customized” CT has several advantages: (1) pts are more likely to be treated with agents that they will respond to, (2) pts can be spared the toxicity of agents that they are resistant to, (3) effective treatment can be delivered early in the course of disease. Methods: We planned a phase II multicentric open label study in two steps (based on Simon design) to evaluate ERCC1 SNPs (T118C and C8092A) and RRM1 SNPs (-37C>A and -524T>C) in advanced NSCLC pts. Here we report the first step for futility. Pts received first line CT according to the assessed ERCC1 and RRM1 SNPs status and the correlated expression levels: treatment A (low ERCC1 and low RRM1) Cisplatin plus Gemcitabine; treatment B (low ERCC1 and high RRM1) Cisplatin plus Docetaxel; treatment C (high ERCC1 and low RRM1) Gemcitabine plus Docetaxel; treatment D (high ERCC1 and high RRM1) Docetaxel plus Vinorelbine. Results: 42 pts were enrolled from Jan. 2010 to Oct. 201, 40 pts received at least 1 cycle of CT; median age was 66 yrs (range 47-73); 33 pts were males; 23(55%) pts were ECOG PS 0, 19(45%) PS 1; all pts had stage IV; 23(55%) pts had adenoca, 13(31%) squamous, 6(14%) other types; 25(62%) pts received treatment A, 3(8%) treatment B, 11(27%) treatment C, 1(3%) treatment D. As primary end-point we assessed the overall best response: 18(45%) pts achieved PR, 12(30%) SD, 8(20%) PD, 2(5%) pts were not evaluable. Updated information on OS and PFS will be presented. CT was well tolerated, there were no treatment related deaths. Conclusions: We observed an improved RR in this setting of NSCLC pts treated with CT according to ERCC1 and RRM1 SNPs status. We are planning to continue the second step of this trial (total 110 pts).