Quantitative analysis of the impact of deepness of response on survival time following patients with metastatic colorectal cancer treated by chemotherapy and anti-EGFR monoclonal antibodies.

Abstract

493 Background: "Deepness of response" (DpR) is a new efficacy outcome measure that could explain the impact of tumor shrinkage on long-term survival outcome. In FIRE-3 trial, OS was significantly longer in patients (pts) treated with FOLFIR plus cetuximab compared with pts who received FOLFIRI plus bevacizumab. One reason was that first-line treatment with Cetximab have a DpR, so it takes a lot of time to grow tumors. The aim of the present analysis was to evaluate OS, PFS, pathological grade and DpR for pts with mCRC treated with anti EGFR antibody+FOLFOX or FOLFIRI. Methods: A total of 100 pts with histopathologically confirmed mCRC treated with first-line chemotherapy in combination with anti-EGFR antibody and second-line chemotherapy with cetximab were enrolled between October 2008 and June 2013. First, we compare DpR for pts with first-line chemotherapy+anti EGFR antibody and second-line chemotherapy+cetximab. Second, we analyzed DpR and pathological grade for 32 pts performed conversion surgery. Third, we compare OS, PFS and DpR for 43 pts treaded with second-line chemotherapy+Cetximab. Results: The 38 (26) pts treated with FOLFOX+cetximab (panitumumab) had a mean DpR of 44.9 (51.4)% (Interquartile range [IR]:36.6 (39.8)%, 60.97 (64.65)%), minimum DpR -45.2 (0)%. The 43 pts treated with second-line FOLFIRI + Cetximab had a mean DpR of 10% (IR:-7.8%, 30.9%) and a minimum DpR of -158%. The DpR wans’t different between first-line FOLFOX+cetximab and panitumumab. But the DpR was significantly different between first-line FOLFOX+cetximab and second-line FOLFIRI+cetximab. Tumor regression grades 0 after preoperative. FOLFOX+cetximab (panitumumab) had a mean DpR of 61.3 (0)%, grade 1 had a mean DpR of 50.83 (56.14)%, grade 2 had a mean DpR of 54.91 (40.5)% and grade 3 had a mean DpR of 58.5 (76)%. Individual DpR of the pts treated with FOLFIRI+cetximab is a significant prognostic factor for survival time (OS and PFS) in the Longest diameter-based models (PFS:p=0.006 OS:p=0.01). Conclusions: Our results emphasize the value of the variable DpR as a new efficacy outcome measure and the DpR was shown to be associated with its ability to prolong OS and PFS.