Patients with advanced non–small cell lung cancer (NSCLC) should receive treatment with erlotinib (Tarceva) before receiving standard chemotherapy only if their tumor is known to harbor EGFR mutations, researchers reported at the 3rd European Lung Cancer Conference in Geneva, Switzerland.1
The recently reported results of biomarker analyses of the TORCH clinical trial confirm that patients with unknown or negative mutation status should be treated with the standard chemotherapy first.
Results of the TORCH Study
The TORCH trial was a randomized phase III trial conducted in Italy and Canada, which compared the efficacy of treatment with the EGFR inhibitor erlotinib, followed at progression of disease by cisplatin and gemcitabine, against the standard reverse sequence.2
The primary endpoint of the original TORCH study was overall survival, and 900 patients were planned. The study was stopped early, however, when the first interim analysis showed that the erlotinib-first regimen was inferior to the standard approach.
In the new study, Ming Tsao, MD, of the Princess Margaret Hospital, and colleagues conducted an exploratory analysis on the TORCH patient tumor samples that were available for analysis, looking for molecular biomarkers known to be potential predictors of benefit from EGFR inhibitors.
The results of this secondary analysis showed a significant interaction in progression-free survival favoring treatment with erlotinib first in patients with EGFR-mutated tumors and favoring treatment with chemotherapy first in patients whose tumors did not express the EGFR mutation.
However they did not observe a significant interaction between treatment efficacy and overall survival. According to Dr Tsao this shows that using erlotinib to treat patients with a mutated tumor is effective, in both the first- and second-line settings; it is more convenient for these patients to receive it as first-line therapy.
Patients with EGFR-mutated tumors benefit from the erlotinib-first regimen because their tumors are very sensitive to the antitumor activity of the drug. According to Dr. Tsao, treatment with erlotinib first should only be applied to patients whose tumor is known to harbor the EGFR mutation. ■
Disclosure: Dr. Tsao reported no potential conflicts of interest.
Expert Point of View: Tetsuya Mitsudomi, MD, PhD
References
1. Tsao MS, Gallo C, Saieg M, et al: Biomarkers of TORCH trial of first-line erlotinib followed by second-line chemotherapy in advanced non-small cell lung cancer patients. European Lung Cancer Conference. Abstract 163O. Presented April 19, 2012.
2. Gridelli C, Ciardiello F, Feld R, et al: International multicenter randomized phase III study of first-line erlotinib followed by second-line cisplatin plus gemcitabine versus first-line cisplatin-gemcitabine followed by second-line erlotinib in advanced non-small cell lung cancer. J Clin Oncol 28(15s):Abstract 7508, 2010.
