192P - Antiangiogenesis-related adverse events (ARAE) to predict efficacy in patients with advanced gastric cancer (AGC) treated with apatinib + chemotherapy: Results from two prospective studies

Background

Studies of apatinib monotherapy suggest that ARAE (proteinuria, hand-foot syndrome [HFS] and hypertension) may predict clinical outcomes in patients with AGC; however, this phenomenon has not been reported in patients receiving apatinib + chemotherapy. We evaluated the potential association between ARAE and efficacy outcomes of apatinib +chemotherapy for AGC.

Methods

We reviewed two prospective trials of patients treated with apatinib + chemotherapy (POF or paclitaxel alone), a phase II study (ESMO-ASIA 2018) and a phase I study (ESMO 2022). POF was paclitaxel 135 mg/m² over 3 h followed by leucovorin 400 mg/m² and oxaliplatin 85 mg/m² over 2 h; then 5-FU 2,400 mg/m² continuous infusion over 46 h. Drugs were started days 1 and 15 of each 28-day cycle. Paclitaxel alone was 80 mg/m² days 1, 8, and 15 of every 28-day cycle. Presence of any ARAE in the first 4 weeks of therapy was assessed and the primary outcome was overall survival (OS). OS was estimated using Kaplan-Meier with the log-rank test. Hazard ratios (HRs) were calculated by univariate and multivariate Cox proportional regression models.

Results

The number of participants was 43 (POF, n=41; paclitaxel alone, n=2). In the first 4 weeks of treatment, 22 (51.2%) had any grade proteinuria, 13 (30.0%) had any grade HFS, and 14 (32.6%) had any grade hypertension. The presence of proteinuria or HFS was associated with prolonged median OS ([months] proteinuria 5.93 vs. 19.10; HR 0.40, 95% CI 0.20-0.79; P=0.0065; HFS 8.92 vs. 22.57 ; HR 0.48, 95% CI 0.23-0.98; P=0.04) and progression-free survival ([PFS] proteinuria 3.50 vs. 9.60 ; HR 0.46, 95% CI 0.23-0.91; P=0.022; HFS 6.40 vs. 10.67 ; HR 0.54, 95% confidence interval (CI) 0.27-1.07; P=0.073 ). 24 (55.8%) patients had one (any grade) proteinuria or HFS in the first 4 weeks, which was associated with prolonged median OS (6.77 vs. 16.35 ; HR 0.47, 95% CI 0.24-0.93; P=0.031) and PFS (4.20 vs. 8.75; HR 0.55, 95% CI 0.28-1.08; P=0.080).

Conclusions

Antiangiogenesis-related proteinuria and HFS may be biomarkers to predict antitumor efficacy of apatinib + chemotherapy in AGC. Future prospective studies are needed to validate findings.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.