Author of

• 12701

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  P3.12 - Poster Session 3 - NSCLC Early Stage (ID 206)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Medical Oncology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/30/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 12725

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    P3.12-024 - A multi-center phase II randomized study of customized neoadjuvant therapy vs. standard chemotherapy (CT) in non-small cell lung cancer (NSCLC) patients with resectable stage IIIA (N2) disease (CONTEST trial) (ID 3107)

    09:30 - 09:30  |  Author(s): F. Merlo
    • Abstract

    Background
    Stage IIIA NSCLC constitutes 30% of all NSCLCs. The most powerful prognostic factors identified in this stage are mediastinal lymph node clearance and a pathologic complete response (pCR). A pCR is obtained in 5-15% of patients (pts) with significant prolongation of survival. The identification of molecular biomarkers, such as excision repair cross-complementation 1 (ERCC1), ribonucleotide reductase subunit M1 (RRM1) and thymidylate synthase (TS), may predict the response to CT. Similarly, EGFR mutations may predict the response to EGFR inhibitors.

    Methods
    CONTEST, a multicenter (19 Italian centers), randomized (2:1), 2-arm, phase II study, will recruit 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. Specimens will be sent to Response Genetics (Los Angeles, CA, USA) for the evaluation of ERCC1, RRM1 and TS using RT-PCR and EGFR using Sanger sequencing. The 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 is pCR, and all randomized pts will be compared by treatment arm. Because pCR is a surrogate endpoint and given the expected proportion of pCRs in the control group (pc= 5%), the minimal clinically worthwhile effect of this customized treatment is an increase to 20%. To detect such an effect at the 0.05 (1-sided) significance level with 80% power, a total of 168 pts (112 in the investigational arm and 56 in the standard arm) will be enrolled. The secondary endpoints are overall survival, disease-free survival, overall survival at 1, 2 and 5 years, overall response and safety. The major eligibility criteria are as follows: histologically confirmed NSCLC appropriate for surgery; ≥18 years old; ECOG performance status (PS) 0-1; sufficient tissue to perform marker analyses; medically fit for resection by lobectomy or pneumonectomy; stage IIIA (N2) patients with technically operable disease limited to T1a, b, T2a, b N2 M0; T3 (>7 cm) N2 M0 are eligible; stage IIIA pts limited to T3 N1 M0, T3 (invasion) N2 M0; T4 N0, N1 M0 are not eligible; NSCLC confirmed by mediastinoscopy; informed consent. This study is open for accrual; further details can be found at ClinicalTrials.gov (NCT01784549). Funded by the Italian Ministry of Health – RF 2009-1530324.

    Results
    N/A

    Conclusion
    N/A