AUTHOR=Tian Hui , Wang Xuan , Lian Bin , Yan Xieqiao , Si Lu , Chi Zhihong , Sheng Xinan , Kong Yan , Mao Lili , Bai Xue , Tang Bixia , Li Siming , Zhou Li , Cui Chuanliang , Guo Jun 

TITLE=Safety Profile of Immunotherapy Combined With Antiangiogenic Therapy in Patients With Melanoma: Analysis of Three Clinical Studies

JOURNAL=Frontiers in Pharmacology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.747416

DOI=10.3389/fphar.2021.747416

ISSN=1663-9812

ABSTRACT=<p><bold>Objective:</bold> To describe the frequency and spectrum of treatment-related adverse events (TRAEs) of immunotherapy combined with antiangiogenic therapy in patients with melanoma.</p><p><bold>Methods:</bold> This retrospective cohort study included three clinical trials on patients with stage III/IV melanoma treated with anti–PD 1 and antiangiogenic therapy.</p><p><bold>Results:</bold> We analyzed data from 72 patients with a median follow-up time of 25.9 months (95% CI, 9.1–42.7 m). The median treatment duration was 7.5 months (range, 0.7–42.8 m), and the median of treatment cycles was 11.0 (range, 1–90). Most patients (70 of 72 or 97.2%) experienced TRAEs (mostly grades 1 or 2). No drug-related deaths were reported. Most TRAEs were hepatic (75%), endocrine (72.2%), skin (65.3%), and gastrointestinal tract (59.7%) manifestations, followed by myelosuppression (55.6%), renal dysfunction (55.6%), and dyslipidaemia (54.2%). The adverse event (AE) spectra were similar between regimens. Using multivariate Cox proportional risk models showed that hypertension was associated with a long PFS. According to our multivariable logistic regression models, TRAEs were not associated with ORR.</p><p><bold>Conclusion:</bold> We found that the prevalence of AEs was higher than that of anti–PD-1 monotherapy. Most of the AEs were mild. The AE spectra were similar to those seen after anti–PD-1 or antiangiogenic therapy monotherapy, without unexpected AEs. Immunotherapy combined with antiangiogenic therapy was well tolerated.</p><p><bold>Clinical Trial Registration</bold>: <ext-link ext-link-type="uri" xlink:href="http://ClinicalTrials.gov" xmlns:xlink="http://www.w3.org/1999/xlink">ClinicalTrials.gov</ext-link>, identifier NCT03955354.</p>