P3.01-085 A Phase 2 Trial of Apatinib in Advanced Non-Squamous NSCLC: Updated Data and Clinical Benefit of Continuing Apatinib after Initial Progression

Abstract

Background: Activated circulating endothelial cells (aCECs) have been indicated as a potential biomarker for cancerous angiogenesis in varieties of malignancies. Furthermore, several studies have exhibited aCECs were related with progression-free survival (PFS) and overall survival (OS) in anti-angiogenesis therapy. Anlotinib is a TKI of VEGFR1/2/3, FGFR1-4, PDGFR a/b, and c-Kit. As a third-line and above treatment on advanced NSCLC, Anlotinib has shown an affirmatory efficacy in ALTER0303 controlled trial. Herein we investigated the connection between aCECs and PFS, OS and metastases burden in the trial. Method: Blood samples were collected at baseline (pre-therapeutically), the 7th, 15th, 21th, 42nd, 63rd day of Anlotinib or placebo. aCECs was measured by Flow Cytometry. Receiver-operating characteristics (ROC) analysis was used to determine a cutoff value of baseline aCECs counts to divide them into high and low groups. The predicting value of aCECs for PFS was investigated by univariate survival analysis. Chi-square test for baseline aCECs counts and patients' clinical characteristics before Anlotinib or placebo treatment was performed. Result: aCECs were obtained in 78 patients (Anlotinib n¼49). No significant difference in baseline characteristics was found between two arms (P>0.05). High baseline aCECs count was statistically in connection with more metastatic lesions (>3) (c 2 ¼ 4.905,P¼0.027). 49 Anlotinib treated patients were divided into 35 and 14 according to the ratio of minimal aCECs counts at every time point and baseline (aCECs min/baseline), as <1 and 1. Median follow-up was 8.6 months. Patients with min/baseline<1 had longer median PFS than ones with min/baseline>1 (193 vs.124 days, HR¼0.439, 95%CI 0.211-0.912, P¼0.023. shown in Table1). However, no significant relation between PFS and aCECs min/baseline was found in control arm. Conclusion: Decreased aCECs during an initial period of Anlotinib therapy may predict longer PFS and baseline aCECs count may be related with the number of metastatic lesions.

Efficacy and safety of apatinib in patients with advanced nonsmall cell lung cancer that failed prior chemotherapy or EGFR-TKIs

“…4. The estimated mPFS of each study was similar to the pooled mPFS value and 95% CI, except for the studies of Zhou et al [15] and Song et al [20] The estimated pooled mPFS was 4.8 months (95% CI, 4.65−4.95) when the study of Zhou et al [15] was omitted, and 4.11 months (95% CI, 3.47−4.77) when the study of Song et al [20]…”

“…A total of 3 studies recorded OS data, [17,18,27] in which single-agent apatinib was administrated to patients with advanced NSCLC in second-line and higher treatment. Zhou et al [15] reported that median OS reached up to 9.26 months. By contrast, the survival data of our pooled analyses were similar to that of anlotinib, another oral TKI targeting VEGFR, PDGFR, FGFR, and c-Kit.…”