Early presence of anti-angiogenesis-related adverse events as a potential biomarker of antitumor efficacy in metastatic gastric cancer patients treated with apatinib: a cohort study

Abstract

BackgroundReliable biomarkers of apatinib response in gastric cancer (GC) are lacking. We investigated the association between early presence of common adverse events (AEs) and clinical outcomes in metastatic GC patients.Patients and methodsWe conducted a retrospective cohort study using data on 269 apatinib-treated GC patients in two clinical trials. AEs were assessed at baseline until 28 days after the last dose of apatinib. Clinical outcomes were compared between patients with and without hypertension (HTN), proteinuria, or hand and foot syndrome (HFS) in the first 4 weeks. Time-to-event variables were assessed using Kaplan–Meier methods and Cox proportional hazard regression models. Binary endpoints were assessed using logistic regression models. Landmark analyses were performed as sensitivity analyses. Predictive model was analyzed, and risk scores were calculated to predict overall survival.ResultsPresence of AEs in the first 4 weeks was associated with prolonged median overall survival (169 vs. 103 days, log-rank p = 0.0039; adjusted hazard ratio (HR) 0.64, 95% confidence interval [CI] 0.64–0.84, p = 0.001), prolonged median progression-free survival (86.5 vs. 62 days, log-rank p = 0.0309; adjusted HR 0.69, 95% CI 0.53–0.91, p = 0.007), and increased disease control rate (54.67 vs. 32.77%; adjusted odds ratio 2.67, p < 0.001). Results remained significant in landmark analyses. The onset of any single AE or any combinations of the AEs were all statistically significantly associated with prolonged OS, except for the presence of proteinuria. An AE-based prediction model and subsequently derived scoring system showed high calibration and discrimination in predicting overall survival.ConclusionPresence of HTN, proteinuria, or HFS during the first cycle of apatinib treatment was a viable biomarker of antitumor efficacy in metastatic GC patients.Electronic supplementary materialThe online version of this article (10.1186/s13045-017-0521-0) contains supplementary material, which is available to authorized users.

Salvage treatment with anlotinib for advanced non‐small cell lung cancer

“…A study of predictive indicators showed that phosphorylated VEGFR2 and hypertension may be predictors of antiangiogenic drugs in breast cancer . A retrospective study identified hypertension, proteinuria, and hand‐foot syndrome emerging during the first cycle of apatinib treatment as viable predictive indicators of efficacy in gastric cancer patients . Girard et al .…”

<p>Apatinib in Patients with Relapsed or Refractory Diffuse Large B Cell Lymphoma: A Phase II, Open-Label, Single-Arm, Prospective Study</p>

“…Interestingly, early occurrence of apatinib-related AEs was reported to be predictive biomarkers for treatment efficacy. 29 Patients with anorexia and grade 2 or worse fatigue and hand-foot syndrome tended to acquire prolonged PFS. 9 Apatinib-related hypertension was also reported to be a valid biomarker for preferable anti-tumour efficacy.…”

A lower apatinib dose provides equivalent efficacy and reduced toxicity: A phase II, single-arm study of apatinib and oral etoposide in metastatic breast cancer

“…In a clinical study of sunitinib in advanced renal cell carcinoma [19], patients with hypertension had longer PFS and OS than patients without hypertension (median OS 41.6 versus 16.4 months, p < 0.0001, medianPFS 12.9 versus 5.6 months, p < 0.0001, respectively). A cohort study of patients with metastatic gastric cancer treated with apatinib showed that the mPFS was prolonged by 24.5 days (86.5 versus 62 days) in patients who developed adverse reactions such as hypertension, proteinuria, and hand-foot syndrome within 4 weeks of taking the drug, and the median OS was extended by 2.2 months [20]. In our study, further analysis showed that the mPFS was prolonged by 4.8 months in patients with hypertension receiving apatinib and etoposide(p = 0.022), and the mPFS in patients with proteinuria was extended by 4.1 months(p = 0.036), but there was no statistically significant difference in overall survival.…”