3666 - The Elderly Patient Individualized Chemotherapy (EPIC) trial, a study for an aged population of non-small cell lung cancer.

Background

Non-small cell lung cancer (NSCLC) is one of the commonest disease worldwide and the leading cause of cancer-related death. Incidence increases with age and reaches a peak in senility, when patients’ (pts) comorbidities may limit the efficacy of treatments. At this time, no homogeneous indications are available for elderly NSCLC pts and the optimization of treatment, with the lowest side effects, is still an unmet need, also after the introduction of innovative drugs. The ribonucleotide reductase catalytic subunit M1(RRM1), the DNA-excision repair protein ERCC1 and the thymidylate synthetase (TS) are cancer molecular markers able to predict response to gemcitabine, platinum compounds and pemetrexd, respectively. Originally, aim of the EPIC study (active from July 2012) was to optimize survival of elderly NSCLC pts with the use of a genomic driven chemotherapy, comparing it to standard treatment. After the proven efficacy of first-line immunotherapy, on June 2018 the protocol was amended with the introduction of a new study arm, aiming to clarify the best strategy in this setting.

Trial design

EPIC is an Italian multicenter, randomized phase III trial, comparing Avelumab (A) vs genomic driven chemotherapy (B) and genomic driven chemotherapy vs standard chemotherapy according to investigator’s choice (C) in elderly untreated NSCLC pts, randomized in a 2:2:1 fashion manner. Age over 70 years, ECOG performance-status 0-1, stage IV non-oncogene addicted NSCLC and tissue availability for gene expression analysis, are key inclusion criteria. Before study entry, pharmacogenomic evaluations of RRM1, ERCC1 and TS is performed in the entire study population, but results are disclosed only to pts randomized in arm B to not influence subsequent treatments in the other arms. Primary endpoint of the EPIC study is overall survival (OS), while secondary endpoints include progression-free survival (PFS) and treatment response rate (by investigator’s assessment). Further objectives are the evaluation of feasibility of treatment selection based on pharmacogenomic parameters, and treatment-related toxicities in every study arm. End of enrollment is expected by the end of 2022.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Department of Oncology - University of Turin, Italy.

Funding

Italian Pharmacology Agency (AIFA).

Disclosure

E. Capelletto: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Boehringer Ingelheim. F. Grossi: Advisory / Consultancy: Eli Lilly; Advisory / Consultancy: Roche; Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Pierre Fabre; Advisory / Consultancy: BMS; Advisory / Consultancy: MSD; Advisory / Consultancy: Novartis. P. Bidoli: Advisory / Consultancy: Eli Lilly; Advisory / Consultancy: Boheringher; Advisory / Consultancy: BMS. O. Caffo: Honoraria (self): Pfizer ; Honoraria (institution): AstraZeneca. S. Novello: Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony: Eli Lilly; Advisory / Consultancy: BMS; Advisory / Consultancy: MSD; Advisory / Consultancy: Roche ; Advisory / Consultancy: Takeda; Advisory / Consultancy: Pfizer; Advisory / Consultancy: AbbVie; Advisory / Consultancy: Celgene. G. Scagliotti: Advisory / Consultancy, Speaker Bureau / Expert testimony: Eli Lilly; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Roche; Advisory / Consultancy: MSD; Advisory / Consultancy: Pfizer. All other authors have declared no conflicts of interest.