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Bepler G , Williams C , Schell MJ , Chen W , Zheng Z , Simon G , Gadgeel S , Zhao XH , Schreiber F , Brahmer J , Chiappori A , Tanvetyanon T , Pinder-Schenck M , Gray J , Haura E , Antonia S , Fischer JR
Randomized International Phase III Trial of ERCC1 and RRM1 Expression-Based Chemotherapy Versus Gemcitabine/Carboplatin in Advanced Non-Small-Cell Lung Cancer
Journal of Clinical Oncology. 2013 Jul;31(19) :2404-2412
PMID: WOS:000330520600020    PMCID: PMC 3691357   
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Abstract
Purpose We assessed whether chemotherapy selection based on in situ ERCC1 and RRM1 protein levels would improve survival in patients with advanced non-small-cell lung cancer (NSCLC). Patients and Methods Eligible patients were randomly assigned 2:1 to the trial's experimental arm, which consisted of gemcitabine/carboplatin if RRM1 and ERCC1 were low, docetaxel/carboplatin if RRM1 was high and ERCC1 was low, gemcitabine/docetaxel if RRM1 was low and ERCC1 was high, and docetaxel/vinorelbine if both were high. In the control arm, patients received gemcitabine/carboplatin. The trial was powered for a 32% improvement in 6-month progression-free survival (PFS). Results Of 331 patients registered, 275 were eligible. The median number of cycles given was four in both arms. A tumor rebiopsy specifically for expression analysis was required in 17% of patients. The median time from informed consent to expression analysis was 11 days. We found no statistically significant differences between the experimental arm and the control arm in PFS (6.1 months v 6.9 months) or overall survival (11.0 months v 11.3 months). A subset analysis revealed that patients with low levels for both proteins who received the same treatment in both treatment arms had a statistically better PFS (P = .02) in the control arm (8.1 months) compared with the experimental arm (5.0 months). Conclusion This demonstrates that protein expression analysis for therapeutic decision making is feasible in newly diagnosed patients with advanced-stage NSCLC. A tumor rebiopsy is safe, required in 17%, and acceptable to 89% (47 of 53) of patients.
Notes
Bepler, Gerold Williams, Charles Schell, Michael J. Chen, Wei Zheng, Zhong Simon, George Gadgeel, Shirish Zhao, Xiuhua Schreiber, Fred Brahmer, Julie Chiappori, Alberto Tanvetyanon, Tawee Pinder-Schenck, Mary Gray, Jhanelle Haura, Eric Antonia, Scott Fischer, Juergen R.