A multicenter phase II randomized study of customized neoadjuvant therapy versus standard chemotherapy (CT) in non-small cell lung cancer (NSCLC) patients with resectable stage IIIA(N2) disease (CONTEST trial).

Abstract

TPS7606 Background: Stage IIIA NSCLC constitutes 30% of all NSCLC patients (pts). The most powerful prognostic factor that has been identified in this stage is clearance of mediastinal lymph nodes and pathologic complete response (pCR). A pCR is obtained in 5-15% of pts with a significant survival prolongation. The identification of molecular biomarkers, such as excision repair cross-complementation 1 (ERCC1), ribonucleotide reductase subunit M1 (RRM1), and thymidylate synthase (TS), may predict response to CT. Similarly, EGFR mutations may predict response to EGFR inhibitors. Methods: CONTEST, a multicenter (19 Italian centers), randomized (2:1) 2-arm phase II study, recruits pts with resectable stage IIIA (N2) NSCLC. Pts will be randomized to receive before resection either standard CT with Cisplatin (CDDP) 75 mg/m2 + Docetaxel (Doc) 75 mg/m2 on day (d) 1 q 21 d for 3 cycles (cys) or customized therapy using predetermined values for ERCC1, RRM1, TS, and EGFR mutations. The choices of customized arms are as follows: -EGFR+: Gefitinib 250 mg/d for 8 weeks. -EGFR-/non-squamous (NS)/TS-/ERCC1-: CDDP 75 mg/m2 + Pemetrexed 500 mg/m2 d 1 q 21 d for 3 cys. -EGFR-/squamous (S) or NS TS+/ERCC1-/RRM1+: CDDP 75 mg/m2 + Doc 75 mg/m2 d 1 q 21 d for 3 cys. -EGFR-/S or NS TS+/ERCC1-/RRM1-: CDDP 75 mg/m2 d 1+ Gemcitabine (Gem) 1250 mg/m2 d 1,8 q 21 d for 3 cys. -EGFR-/S or NS TS+/ERCC1+/RRM1+: Doc 75 mg/m2 d 1 + Vinorelbine 20 mg/m2 d 1,8 q 21 d for 3 cys. -EGFR-/S or NS TS+/ERCC1+/RRM1-: Doc 40 mg/m2 y 1, 8 + Gem 1200 mg/m2 d 1,8 q 21 d for 3 cys. The primary end point will be obtained by comparing the pCR in all randomized pts based on treatment arm. Because pCR is a surrogate endpoint and given the expected proportion of pCR's in the control group pc= 5%, the minimal clinically worthwhile effect of this customized treatment is an increase in this proportion to 20%. To detect such an effect at the 0.05 (1-sided) significance level with 80% power, a total of 168 pts will be enrolled. This study is open for accrual; further details can be found on ClinicalTrials.gov (NCT01784549). Funded by Italian Ministry of Health – RF 2009-1530324. Clinical trial information: NCT01784549.