e16092 Background: It has been extremely challenging to identify suitable predictive or prognostic factors of anti-VEGF agents. Apatinib, a vascular endothelial growth factor receptor 2(VEGFR-2) inhibitor, showed promising efficacy in chemo-refractory metastatic colorectal cancer (mCRC) patients in a phase II trial. The aim of current study was to identify the potential predictive and prognostic factors of apatinib in this phase II trial. Methods: A total of 48 patients with mCRC who had failed from standard fluorouracil-containing chemotherapies were recruited in this prospective single-arm study. Apatinib at a 500mg dose was administered daily continuously. Clinical parameters, including patients background, biochemical parameters at baseline, tumor markers at baseline and day 28, and adverse events in initial 28 days were evaluated to identify predictive and prognostic factors. The median neutrophil/lymphocyte ratio (NLR) was adopted as a cutoff value to discriminate patients with low versus high NLR. Early tumor marker decrease was defined as an abnormal parameter with a decrease of > 10% by day 28. This study is registered with the Chinese Clinical Trial Registry, number ChiCTR1900020503. Results: Patients characteristics were not associated with differences in PFS and OS. Seven (14.6%) and 11 (22.9%) patients had initial normal CEA and CA19-9, respectively, and were excluded from the analysis of tumor markers. The median NLR were 4.1. In univariate analysis, low baseline NLR, early CA19-9 decrease, and the hand-foot syndrome (HFS) were associated with good progression-free survival (PFS) [NLR, HR 0.38 (95% CI 0.16–0.89), P = 0.027; CA19-9, HR 0.37 (95% CI 0.16-0.83), P = 0.016; HFS HR 0.23 (95% CI 0.08-0.68, P = 0.007); respectively]. Low baseline NLR and early CA19-9 decrease were also associated with good overall survival (OS) [NLR, HR 0.34 (95% CI 0.17–0.67), P = 0.002; CA19-9, HR 0.46 (95% CI 0.23-0.95), P = 0.035; respectively]. NLR and HFS retained a significant association with PFS [NLR, HR 0.36 (95% CI 0.15–0.84), P = 0.019; HFS, HR 0.25 (95% CI 0.08–0.77), P = 0.016; respectively] while only NLR retained a significant association with OS [NLR, HR 0.35 (95% CI 0.17–0.70), P = 0.019] in the multivariate analysis using the aforementioned factors. Conclusions: Clinical parameters including low baseline NLR, early CA19-9 decrease and HFS could be positive predictive factors of the efficacy of apatinib in mCRC. NLR could be the independent prognostic factor of OS in mCRC. Additional studies are warranted for further validation.
Usefulness of 18F-FDG PET/CT, LDH and tumor markers in the prognosis and evaluation of tumor response after RMB therapy in advanced, metastatic colorectal cancer (mCRC)