REOX: Effectiveness evaluation of re-exposure to oxaliplatin in patients with metastatic colorectal cancer.

Abstract

764 Background: Colorectal cancer has high incidence and mortality rates. Treatment of metastatic colorectal adenocarcinoma has evolved since the approval of irinotecan, oxaliplatin and monoclonal antibodies with survival surpassing 30 months in contemporary trials. Nevertheless there is paucity of effective options after failure of these protocols. Thus re-exposure to previously used drugs became a treatment strategy. We aimed to evaluate the efficacy of retreatment with oxaliplatin in mCRC and its correlation with clinicopathological features. Methods: We retrospectively analyzed 83 patients with mCRC who underwent REOX treated at a single cancer center in Brazil. REOX was defined as a second trial of an oxaliplatin containing regimen after a previous failure. Primary endpoint was time to treatment failure (TTF) after REOX. Results: Median age of our cohort was 53.5y. Female/Male: 51.8%/48.2%. Primary colon was found in 67.5% while 32.5% had primary rectal adenocarcinoma. KRAS status was wild type in 57.8% and mutated in 39.8%. Exclusive hepatic metastasis was found in 19.3%. Median follow-up after REOX was 31m. Main chemotherapy regimen was mFOLFOX6 (84.3%). Bevacizumab and Cetuximab were used in 42.2% and 6% respectively. Most patients underwent REOX in third and fourth lines, 48.2% and 25.3% respectively. Median time to treatment failure (mTTF) after REOX was 6.04m. Overall survival was 10.04m. Disease control (CR + PR + SD) was observed in 56.6%, while 42.2% had progressive disease (PD). Reasons for interruption were as follows: PD (68.7%), toxicity (19.3%) and metastasectomy (2.4%). Patients who attained disease control had better OS (14.5m) compared with patients who had PD (14.5m versus 6.24m, p < 0.0001). Patients with exclusive hepatic metastasis had a trend to a better TTF compared to other metastasis sites (8.96m X 6.01m, p = 0.2). Regarding KRAS status, there was no difference in mTTF (wt 6.68m, mut 6.04m, p = 0.14). Conclusions: In the setting of pretreated mCRC patients where there are few options available, REOX remains an effective treatment, with mTTF of 6.04m in our cohort. This could be related to progression of cell clones sensitive to the drug after a time lapse since the previous exposure.