463PD - Clinical factors influencing outcome in metastatic colorectal cancer (mCRC) patients treated with fluoropyrimidine and bevacizumab (FP + Bev) maintenance treatment (Tx) vs observation: A pooled analysis of the phase 3 CAIRO3 and AIO 0207 trials

Abstract

The CAIRO3 and AIO 0207 studies showed that first-line maintenance Tx with FP + Bev vs observation after FP + oxaliplatin(Ox) + Bev induction Tx in mCRC patients is effective, while quality of life is maintained. We performed a pooled analysis and aimed to identify subgroups with clinical characteristics that benefit most from FP + Bev maintenance Tx. A total of 871 mCRC patients (CAIRO3: n = 557; two arms of AIO 0207: n = 314) that received FP + Bev maintenance Tx vs observation were analyzed. We analyzed whether Tx effect was modified by 12 clinical characteristics: sex; age; performance status; response to induction Tx; stage; primary tumor site and resection status; number of metastatic sites; synchronous vs metachronous mCRC; LDH at randomization; platelet count and CEA at start of induction Tx. We used mixed effects Cox models with study as random intercept and baseline covariables and treatment as fixed effects. Time to 1st progression (PFS1), time to 2nd progression after FP + Ox + Bev reintroduction (PFS2, primary endpoint of both studies) and overall survival (OS) were analyzed. FP + Bev maintenance Tx compared to observation resulted in a highly significant benefit in PFS1 (HR 0.40 [95% CI 0.34 - 0.47]) and PFS2 (HR 0.68 [95% CI 0.59 - 0.80]), which was observed in all investigated subgroups. OS results showed a marked heterogeneity between the two studies, for yet unknown reasons, and remained not significant in the pooled analysis (HR 0.90 [95% CI 0.76 – 1.05]). Patients with elevated platelet count (> 400 x 109/L) at start of induction Tx had significantly more benefit from FP + Bev maintenance Tx vs observation in PFS1 (HR 0.31 [95% CI 0.23 - 0.41] vs HR 0.45 [95% CI 0.37 - 0.55]) and PFS2 (HR 0.53 [95% CI 0.40 - 0.70] vs HR 0.76 [95% CI 0.63 - 0.92]). Tests for interaction were p < 0.05. This pooled analysis confirms the benefit of FP + Bev maintenance Tx compared to observation in the first-line Tx of mCRC. This benefit was observed in all subgroups that were investigated. We identified platelet count at start of induction Tx to be a significant predictive factor for efficacy of FP + Bev maintenance Tx.