Early tumor shrinkage (ETS) and deepness of response (DoR) to predict progression-free, postprogression, and overall survival: Results from the phase III TRIBE trial.

Abstract

521 Background: The TRIBE trial demonstrated that first-line FOLFOXIRI plus bevacizumab (bev) improves PFS, response rate (RECIST), and OS in comparison to FOLFIRI plus bev (ASCO Annual Meeting 2013). Recent experiences evidenced that both ETS and DoR may implement the assessment of response and correlate with survival in metastatic colorectal cancer (mCRC). Methods: ETS was defined as the relative change in the sum of longest diameters of RECIST target lesions at week 8 compared to baseline. A 20% decrease was adopted as cut-off value to discriminate early responders and non-responders. DoR was defined as the relative change in the sum of longest diameters of RECIST target lesions at the nadir in the absence of new lesions or progression of non-target lesions compared to baseline. The median value was used as cut-off. Results: Out of 508 randomized patients, 443 and 484 patients were evaluable for ETS and DoR, respectively. Early responders achieved longer PFS (median PFS: 12.7 vs 10.0 mos, HR: 0.66 [0.52-0.79], p<0.0001), post-progression survival (median PPS: 17.1 vs 10.7 mos, HR: 0.64 [0.47-0.81], p=0.0005) and OS (median OS: 35.8 vs 22.4 mos, HR: 0.54 [0.39-0.67], p<0.0001). Patients achieving a DoR higher than the median reported longer PFS (median PFS: 13.1 vs 9.3 mos, HR: 0.61 [0.49-0.73], p<0.0001), PPS (median PPS: 18.4 vs 10.5 mos, HR: 0.58 [0.44-0.73], p<0.0001) and OS (median OS: 36.8 vs 21.3 mos, HR: 0.47 [0.35-0.58], p<0.0001). A significant correlation of DoR as a continuous variable with PFS (HR: 0.983 [0.979-0.986], p<0.0001), PPS (HR: 0.987 [0.984-0.991], p<0.0001) and OS (HR: 0.979 [0.975-0.983], p<0.0001) was observed. No differences across arms were reported. Conclusions: ETS and DoR predict PFS, PPS and OS. These findings support the hypothesis that the adoption of active upfront regimens, able to induce a rapid and deep tumor shrinkage, may positively affect the subsequent disease history, thus translating into an advantage in survival. Clinical trial information: NCT00719797.