Author of

• 10743

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  P1.10 - Poster Session 1 - Chemotherapy (ID 204)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Medical Oncology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/28/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 10799

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    P1.10-056 - The Elderly Patient Individualized Chemotherapy Trial (EPIC): A Randomized Phase III Multicenter Trial of Customized Chemotherapy versus Standard of Care for 1st Line Treatment of Elderly Patients with Advanced Non-Small-Cell Lung Cancer (ID 1117)

    09:30 - 09:30  |  Author(s): L. Cordero
    • Abstract

    Background
    This is an ongoing phase III multicenter randomized trial comparing first line pharmacogenomic-driven chemotherapy based on Excision-Repair-Cross-Complementing-1 (ERCC1), Ribonucleotide Reductase subunit M1 (RRM1) and Thymidylate Synthase (TS) gene expression, versus standard first line treatment in elderly patients (pts) with advanced non-small-cell lung cancer (NSCLC). Chemotherapy selection based on an individual patient’s molecular profile is a potentially promising approach to optimize efficacy with the already available cytotoxic drugs. In older pts this is particularly relevant owing to their rapid deterioration of symptoms and their increased propensity to suffer therapy-induced toxicity.

    Methods
    Pts aged >70 years, with ECOG Performance Status (PS) 0 or 1, previously untreated for stage IV NSCLC will be evaluated. In a 2:1 fashion, pts will be randomized to experimental arm (A) or standard arm (B). They must have measurable disease and EGFR negative mutational status. In arm A, treatment with single or dual-agent chemotherapy will be based on histology, ERCC1 (E), RRM1 (R) and TS (T) expression at the mRNA level. Expression of E, R and T is assessed by qRT-PCR on paraffin-embedded tumor specimens in a central laboratory. The cut off for high or low expression have been previously defined. Pts with squamous NSCLC who are: E low/R high will be treated with single agent carboplatin, E high/R low with single agent gemcitabine, E low/R low with carboplatin and gemcitabine and E high/R high with docetaxel or vinorelbine. In non-squamous NSCLC pts: E low/T high will be treated with carboplatin, E high/T low with pemetrexed, E low/T low with carboplatin and pemetrexed, E high/T high/R low with gemcitabine and E high/T high/R high with docetaxel or vinorelbine. In arm B treatment will be standard of care at the discretion of the care provider. The primary endpoint is overall survival (OS). The secondary endpoints are progression-free survival (PFS), disease response according to RECIST 1.1 and tolerability (using CTCAE version 4.0). Feasibility of treatment selection based on pharmacogenomic parameters will also be assessed. Treatment will continue to a maximum of 6 cycles if tolerated or until disease progression. Switch maintenance treatment is not allowed in either arm. Continuation maintenance (one or more of the agents used in the initial regimen) is allowed at the discretion of the investigator. Treatment upon progression is at the discretion of the care provider. Assuming an exponential survival distribution for both treatment arms and a median survival time of 8 months in the control arm we anticipate to detect an improvement of 3 months in the median survival time in the experimental arm. To have 90% power to detect a three-month improvement in median survival at a significance level of 5% (2-sided) and assuming a 10% failure rate in gene analyses or loss to follow up rate, a sample size of 567 patients is planned to be enrolled.

    Results
    Not Applicable

    Conclusion
    We hypothesize that such tailored approach will improve survival decreasing the exposure to ineffective toxic agents in advanced NSCLC elderly pts. To our knowledge this is the first pharmacogenomic-driven randomized trial in this population.