P-167 Cetuximab rechallenge in metastatic colorectal cancer patients

Abstract

Introduction:Worldwide, metastatic colorectal cancer (mCRC) has a 5-year-survival of 6%. The introduction of oxaliplatin, irinotecan and biologic therapies allowed a median overall survival of 24 months. Nowadays the combination of chemotherapy and monoclonal antibodies is recommended. It's known that K-RAS mutation is an early pathogenic step in colorectal development, and it remains the same during disease's history. After first progression to anti-EGFR therapy, it can occur expansion of K-RAS wild-type clones, which will constitute the major part of the tumor mass at the following progression of disease, leading to tumor sensitivity to rechallenge. Methods: Retrospectively, we analyzed patients diagnosed with K-RAS wild-type mCRC from January 2010 to December 2015, treated with cetuximab - plus irinotecan-based therapy, who had disease's progression for which underwent a line of chemotherapy, and after a new disease's progression, were retreated with cetuximab plus irinotecan-based therapy (rechallenge).We assessed both treatment efficacy and safety. Results: All 15 patients, 8 females and 7 males, had a median diagnosis age of 57 years (40-74 years) and a good performance status (ECOG 0 or 1). The most frequent comorbidity was high blood pressure (26.6%). Primary tumor site was colon in 66.6% and rectum in 33.3%. Most patients had 2 sites of metastasis (66.7%). The most common site of metastasis were liver (60%), lung (40%), nodes (33%) and ovary (13%). 73.3% was submitted to metastasectomy (liver, lung and ovary metastasis). Until rechallenge, patients underwent a median of 4 (2-6) therapeutic lines, including cetuximab containing regimen. The median time between last cycle of first cetuximab based therapy and first cycle of the following cetuximab retreatment was 7.7 months (1.6-30). During the first cetuximab regimen, FOLFIRI was used in 60% and Irinotecan monotherapy in 40%, the median number of cycles was 9 (3-20). Disease progression occurred in 40%, partial response in 20% and disease stabilization in 40% of patients. Median progression-free survival was 10 months. As for cetuximab rechallenge, the chemotherapy chosen was Irinotecan monotherapy in 73.3% and FOLFIRI in 26.7 %, median number of cycles was 7 (2-25). Three patients are still ongoing cetuximab based regimen. Response evaluation revealed 46.7% of progression, 13.3% partial response and 26.7% disease stabilization. Median progression-free survival was of 3.5 months. 25% of patients had the same response in both first and rechallenge settings and 20% had an improved response. Most patients had skin toxicity grade 1/2 (86.7%), but there were 2 cases of grade 3 toxicity, one of which lead to dose adjustment of cetuximab. Hypomagnesemia occurred in 26.7% of patients. The median overall survival was 36.9 months. Conclusion: There is an apparent benefit of cetuximab rechallenge in disease stabilization and overall survival with little negative impact on quality of life. This leads us to think that this strategy will have an important role by delaying the progression of disease, as seen in current phase II studies.