P-73 Clinical prognostic factors for overall survival and time to progression in RAS-wild type metastatic colorectal cancer treated with anti-EGFR monoclonal antibodies as third or subsequent-line therapy

Abstract

Survival from metastatic colorectal cancer (mCRC) has improved with the use of anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibodies. However, one in four patients treated with it as a third or subsequent line therapy will not benefit. This study aims to identify prognostic factors for overall survival (OS) and time to progression (TTP) in Ras-wild type (RAS WT) colorectal cancer treated with anti-EGFR monoclonal antibodies as third or subsequent line therapy. This retrospective analysis included patients with RAS WT mCRC treated with cetuximab or panitumumab as third or subsequent line therapy between 2012 and 2017 at Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology. Multivariate Cox proportional regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for OS and TTP. A total of 162 patients were included in the study. Median age at diagnosis was 65 years, 87 (53,7%) patients were male. Median OS and TTP were 10.9 months and 4.1 months, respectively. Among 134 (83%) pts evaluable for response, there were 35 (26%) partial responses (PRs), 50 (37%) pts with SD and 49 (37%) pts with PD. No differences in OS and TTP were observed between cetuximab and panitumumab. A significantly worse prognosis in terms of OS was observed for patients with peritoneal metastasis (HRs = 2.54, p=0.01). There was also a trend towards worse overall survival in patients with lung metastasis (p= 0.07) and those with elevated serum alkaline phosphatase levels (p= 0.06). Factors associated with shorter TTP were lung metastasis (HRs = 1.63, p=0.02) and ECOG performance status (PS) greater than or equal to 2 (HRs = 2.58, p=0.002). A significantly better prognosis in terms of both OS and TTP was observed for patients with body mass index (BMI) above 25 kg/m2 [HRs = 0.5 (p=0.01) and 0.66 (p=0.049), respectively]. Taking into account the presence of visceral metastases, lung metastases, elevated serum ALKP and BMI<25, we constructed a new prognostic model by combining these prognostic variables in the following way: low-risk group (0 adverse factors); intermediate group (1-2 factors); high-risk group (3-4 factors). Median survival duration for low, intermediate, and high-risk groups were 15.4 months, 11.4 months, and 5.6 months, respectively. Patients from the low-risk group had significantly better survival than those in high-risk group (HR 0,41; CI 95% 0,232-0,711; p=0,002). Anti-EGFR antibodies are effective as the third or subsequent-line therapy in RAS WT mCRC patients. Patients with peritoneal metastasis showed worse prognosis in terms of OS, whereas lung metastasis and ECOG PS ≥2 were associated with shorter TTP. Our novel prognostic model was able to efficiently identify 3 groups of patients with significantly different OS outcomes.