An international, multicenter, randomized phase III study of first-line erlotinib followed by second-line cisplatin/gemcitabine versus first-line cisplatin/gemcitabine followed by second-line erlotinib in advanced non-small-cell lung cancer: treatment rationale and protocol dynamics of the TORCH trial.

Herein, we present a randomized phase III Italian-Canadian trial named TORCH (Tarceva or Chemotherapy). In TORCH, we are investigating whether erlotinib as first-line therapy until progression followed by chemotherapy with cisplatin/gemcitabine will not be inferior in terms of survival to the standard arm, consisting of first-line cisplatin/gemcitabine for 6 cycles, followed at progression by erlotinib until second progression. The primary objective is overall survival, and an adjunctive primary endpoint is activity of first-line treatment with erlotinib in terms of progression-free rate after 9 weeks of treatment. Secondary objectives include response rate, progression-free survival, toxicity, quality of life, and exploratory evaluations of tumor tissue and blood samples for biologic or genomic determinants of outcome. The study design is based on a noninferiority survival comparison with about 900 patients expected to be recruited. An early analysis of activity will be performed in the experimental arm (first-line erlotinib followed by chemotherapy).