1329TiP - A randomized Phase III multicenter trial of customized chemotherapy versus standard of care for 1st line treatment of elderly patients with advance...

Date 27 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anti-Cancer Agents & Biologic Therapy
Geriatric Oncology
Non-Small-Cell Lung Cancer, Metastatic
Presenter Tiziana Vavala
Citation Annals of Oncology (2014) 25 (suppl_4): iv426-iv470. 10.1093/annonc/mdu349
Authors T. Vavala1, S. Novello2, F. Grossi3, A. Misino4, D. Cortinovis5, G. Valmadre6, G. Meoni7, O. Caffo8, A. Follador9, A. Bearz10, P. Trenta11, V. Gregorc12, C. Defferrari13, L. Cordero14, I. Colantonio15, V. Torri16, V. Monica1, M. Papotti1, G. Scagliotti1
  • 1Department Of Oncology, University of Turin AOU San Luigi, 10043 - Orbassano (TO)/IT
  • 2Department Of Oncology, University of Turin AOU San Luigi, Orbassano (TO)/IT
  • 3Medical Oncology A, National Institute for Cancer Research, Genoa/IT
  • 4Department Of Medical Oncology, National Cancer Research Centre "Giovanni Paolo II", Bari/IT
  • 5Dept. Of Medical Oncology, Azienda Ospedaliera S. GerardoU.O. Oncologia Medica, IT-20052 - Monza/IT
  • 6Dept. Of Internal Medicine And Hematology, Ospedale E. Morelli AOVVAzienda Ospedaliera Valtellina e Valchiavenna, IT-23039 - Sondalo/IT
  • 7Medical Oncology Unit, Azienda Ospedaliero Universitaria Careggi, 50134 - Firenze/IT
  • 8Oncology Department, Ospedale Sta Chiara, 38100 - Trento/IT
  • 9Oncologia, Azienda Ospedaliera Universitaria-UdineSta Maria della Misericordia, IT-33100 - Udine/IT
  • 10Department Of Medical Oncology, Cro National Institute for Cancer Research, Aviano/IT
  • 11Department Of Radiology, Oncology And Human Pathology, Sapienza University of Rome, 00161 - Rome/IT
  • 12Oncologia, IRCCS San Raffaele, 20132 - Milano/IT
  • 13Medical Oncology Unit, Galliera Hospital, Genova/IT
  • 14Oncopneumology Department, AO Sassari, Sassari/IT
  • 15Medical Oncology Department, AO Santa Croce e Carle, Cuneo/IT
  • 16Department Of Oncology, Mario Negri Institute, Milan/IT

Abstract

Background

Phase III trial aiming to compare first line pharmacogenomic-driven chemotherapy based on Excision-Repair-Cross-Complementing-1 (ERCC1, E), Ribonucleotide Reductase subunit M1 (RRM1, R) and Thymidylate Synthase (TS, T) gene expression versus standard treatment in elderly patients (pts) with advanced NSCLC.

Trial design

pts aged ≥70 years, ECOG Performance Status 0 or 1, EGFR negative mutational status, chemonaïve stage IV NSCLC will be evaluated. Pts will be randomized (2:1) to experimental arm (A) or standard arm (B). In arm A, treatment will be based on histology, E, R and T mRNA expression. The cut-off for high or low expression have been previously defined. Treatments for pts with squamous NSCLC: carboplatin for E low/R high, gemcitabine for E high/R low, carboplatin and gemcitabine for E low/R low, docetaxel or vinorelbine for E high/R high. Treatments for non-squamous NSCLC pts: carboplatin for E low/T high, pemetrexed for E high/T low, carboplatin and pemetrexed for E low/T low, gemcitabine for E high/T high/R low, docetaxel or vinorelbine for E high/T high/R high. In arm B treatment will be at the investigator discretion. The primary endpoint is overall survival. The secondary endpoints are progression-free survival, response rate (RECIST 1.1) and tolerability (CTCAE version 4.0). Feasibility of treatment selection based on pharmacogenomic parameters will be also assessed. Treatment will continue to a maximum of 6 cycles if tolerated or until disease progression. Assuming an exponential survival distribution for both 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.

Conclusion

To our knowledge, this is the first prospective pharmacogenomic-driven trial designed in elderly advanced NSCLC population.

Disclosure

D. Cortinovis: Consultant for AZ, BI, Roche and Lilly; M. Papotti: Honoraria have been received from Eli Lilly; G. Scagliotti: Honoraria have been received from Eli Lilly, Roche, Pfizer and Astrazeneca. All other authors have declared no conflicts of interest.