The rationale behind the search for early signals of treatment efficacy is to improve treatment decisions as well as to potentially expedite drug development. Two presentations at ASCO 2014 showed evidence that early clinical responses may correlate with overall survival (OS). In the ARCAD meta-analysis of 16 phase 3 trials that included nearly 11,000 patients with mCRC who were treated with first-line chemotherapy (5-FU/leucovorin/capecitabine +/- oxaliplatin/irinotecan), early tumor shrinkage (ETS; ?20% decrease from baseline), early objective tumor response (EOTR using RECIST criteria), early nonprogression status (EnPD by RECIST) at 6, 8, or 12 weeks were compared with OS (Sommeijer D, et al. ASCO 2014. Abstract 3538). ETS and EOTR were significant predictors of OS with hazard ratios (HRs) ranging from 0.60 to 0.64 (P <.0001), even when the data were adjusted for age, performance status, number of metastases, and prior treatment.
In a similar presentation, ETS and EOTR were compared with the standard best overall response and confirmed response in a meta-analysis of 8 randomized clinical trials with 4776 patients with mCRC treated with first-line chemotherapy plus an antiangiogenic (bevacizumab and/or cediranib) (Saad ED, et al. ASCO 2014. Abstract 3578). At 6, 8, and 12 weeks, ETS and EOTR were significantly associated with PFS and OS (P ?.001 for all HRs).
Both of these studies suggest that the prediction performance of these early-response endpoints may be valid in making early treatment decisions for patients with mCRC.
