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.
Highlights
Reliable biomarkers of apatinib response in gastric cancer (GC) are lacking
Presence of aAdverse events (AE) 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 [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)
The onset of any single AE or any combinations of the AEs were all statistically significantly associated with prolonged overall survival (OS), except for the presence of proteinuria
Summary
Reliable 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. Gastric cancer (GC) is the fourth most common cancer and the second leading cause of cancer-related deaths worldwide, with more than 700,000 deaths annually [1]. China has almost 42% of the GC cases worldwide. There are about 679,000 new cases and 498,000 GC related deaths in China [2], which is a heavy burden to public health. First-line chemotherapy provides a 6-month survival benefit for patients with advanced GC, second-line chemotherapy with irinotecan or docetaxel adds only about 1.5 months to OS [3, 4]. The recent REGARD [5] and RAINBOW [6] trials has led to the approval of ramucirumab (a monoclonal antibody VEGFR-2 antagonist) alone and in combination with paclitaxel, in second-line treatment of GC. There is no standard third-line treatment if second-line chemotherapy fails
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