PROX: Primary resistance to oxaliplatin containing regimen in the first line treatment of metastatic colorectal carcinoma—Retrospective analysis.

Abstract

855 Background: The rate of primary resistance to modern first line (FL) chemotherapy regimen in the treatment of metastatic colorectal cancer (mCRC) is low. Progression Disease (PD) to FOLFOX in the FL is less than 15% in most trials. Prognostic factors associated with worse outcome in mCRC have been identified. However, primary resistance to Oxaliplatin (PROX) containing regimen is not well understood, as well as the role of salvage therapy in further lines of treatment. The aim of the study was to analyze clinical and pathological characteristics of patients with PROX. Methods: A retrospective, single center study included patients that presented PD in the first response evaluation with an Oxaliplatin containing regimen in the FL treatment of mCRC. We also evaluated the Overall Survival (OS) and progression free survival (PFS) of these patients to second and third line. Clinical and pathological variables were analyzed and correlated with (OS). Results: A total of 55 patients were inclued. Median age these cohort was 57 years. Female/Male rate was 42%/58%. Mucinous component was 27%. Right and Left colon was 27% and 66%, respectively. BRAF mutation (2/16 pts). Wild type KRAS was 44%. Synchronic metastasis was 75%. Ressection of metastasis was performed in 20%. Liver limeted disease was found in 45%. Main chemotherapy regimen containing oxaliplatin was FOLFOX (78%) in first line. Bevacizumab, Cetuximab and Panitumumab were used in 21.8%, 9%, 1.8%, respectively. OS was 9.4 months. PFS in second line 3.8 months (47 pts) and third line 3.5 months (18 pts). The only variable associated with longer survival was resection of metastasis (25.6 x 8.6 months, p=0.039). Conclusions: No clinical and pathological variable were able to predict primary resistance to Oxaliplatin containing regimen. However, we found a higher proportion of mucinous subtype. Patients submitted to resection of metastasis had almost three fold the survival of patient that did not underwent surgery. Refractory patients have a very short survival. Further lines of treatment are not able to rescue these patients. Further studies focusing in patients with primary resistance to chemotherapy in first line are needed.