1646PD - Customized first line chemotherapy according to ERCC1 and RRM1 SNPS in advanced non-small-cell lung cancer (NSCLC) patients: a phase II study

Date 01 October 2012
Event ESMO Congress 2012
Session Basic Science and Translational Research II
Topics Biomarkers
Non-Small-Cell Lung Cancer, Locally Advanced
Presenter Francesca Mazzoni
Authors F. Mazzoni1, G. Meoni1, F.L. Cecere1, C. Giuliani2, A. Camerini3, G. Allegrini4, F. Martella5, L. Boni6, F. Torricelli2, F. Di Costanzo7
  • 1Medical Oncology Unit, Azienda Ospedaliero Universitaria Careggi, 50134 - Firenze/IT
  • 2Genetic Diagnosis Laboratory, AOU Careggi, 50134 - Firenze/IT
  • 3Medical Oncology Unit, Versilia Hospital, Viareggio/IT
  • 4Medical Oncology Unit, Pontedera Hospital, Pontedera/IT
  • 5Ospedale di S. Maria Annunziata, 50100 - Bagno a Ripoli/IT
  • 6Centro Coordinamento Sperimentazioni Cliniche, ITT-AOU Careggi, 50134 - firenze/IT
  • 7Azienda Ospedaliero Universitaria Careggi, 50134 - Firenze/IT

Abstract

Introduction

Excision repair cross complementation group 1 (ERCC1) and ribonucleotide reductase 1 (RRM1) expression levels are predictive of chemotherapy (CT) efficacy in some malignancies. Customized CT has several advantages: patients (pts) are more likely to be treated with agents that they will respond to, pts can be spared the toxicity of agents that they are resistant to.

Methods

We planned a phase II multicentric trial in two steps based on Simon design. Pts affected by advanced NSCLC are treated with first line CT according to Single Nucleotide Polymorphisms (SNPs) of ERCC1 (T118C and C8092A) and RRM1 (-37C > A and -524T > C), which are supposed to be correlated with specific expression levels. CT is delivered as follow: treatment A (low ERCC1 and RRM1) Cisplatin plus Gemcitabine; treatment B (low ERCC1, high RRM1) Cisplatin plus Docetaxel; treatment C (high ERCC1, low RRM1) Gemcitabine plus Docetaxel; treatment D (high ERCC1 and RRM1) Docetaxel plus Vinorelbine.

Results

Here we report the first step analysis for futility: 42 pts were enrolled from January 2010 to November 2011; 40 pts received at least 1 cycle of CT; median age was 66 years (range 47-72); 30(75%) pts were males; 21(52%) pts showed ECOG PS 0, 19(48%) PS 1; 36(90%) pts had stage IV and 4(10%) IIIB; 23(58%) pts had adenocarcinoma, 14(35%) squamous, 3(7%) 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 and found a 55% response rate (RR) [38.7 – 70.4, 95% CI] in the intention to treat population. Subgroups analysis showed 46.2% RR in non squamous pts and 71.4% RR in squamous pts. Secondary end-points were progression free survival (PFS), overall survival (OS) and safety. The median follow-up time is 7.1 months, 12 pts did not show progression disease and 23 pts are still alive, then data for PFS and OS are not mature. CT was well tolerated: only 17(42%) pts showed grade 3-4 toxicity and there were no treatment related deaths.

Conclusions

We observed an increase of RR in advanced NSCLC pts treated with CT according to ERCC1 and RRM1 SNPs status, the treatment strategy overcomes the first step of the study.

Disclosure

All authors have declared no conflicts of interest.