Abstract
Objective: To describe the frequency and spectrum of treatment-related adverse events (TRAEs) of immunotherapy combined with antiangiogenic therapy in patients with melanoma. Methods: This retrospective cohort study included three clinical trials on patients with stage III/IV melanoma treated with anti–PD 1 and antiangiogenic therapy. Results: 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. Conclusion: 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. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT03955354.
Highlights
Melanoma is an aggressive malignancy with a dismal prognosis
The adverse event (AE) spectrum of combination therapy is thought to differ from that of the anti–PD-1/-PD-L1 regimen, but the available evidence is mainly derived from a series of small prospective studies (Sheng et al, 2019)
All data in this study are derived from patients treated with at least one cycle of anti–PD-1 plus antiangiogenic therapy enrolled in one of the following clinical trials performed at the Peking University Cancer Hospital: (1) a phase IB nonrandomized, open-label, dose-finding trial on patients with metastatic mucosal melanoma (n 33, patients received toripalimab plus axitinib, ClinicalTrials.gov identifier: NCT03086174); (2) a phase II randomized, open-label, multicenter trial on first-line treatment of patients with metastatic mucosal melanoma; and (3) a phase II study on first-line treatment of patients with unresectable stage III or IV acral melanoma (n 30, patients received camrelizumab plus apatinib, ClinicalTrials.gov identifier: NCT03955354)
Summary
Melanoma is an aggressive malignancy with a dismal prognosis. The incidence of melanoma has increased annually (Miller et al, 2019; Miller et al, 2020). Some prospective studies have shown that immunology greatly improved the clinical outcomes of patients with cutaneous advanced melanoma (Hodi et al, 2010; Wolchok et al, 2015; Robert et al, 2019). The National Comprehensive Cancer Network (NCCN) recommends anti–PD-1 monotherapy as the standard treatment for advanced cutaneous melanoma in its clinical practice guidelines. Anti–PD-1 as monotherapy does not provide the same survival benefits in patients with acral and mucosal melanoma as it does in patients with cutaneous melanomas (Tang et al, 2020). A phase Ib trial showed a survival benefit from combination therapy in patients with advanced mucosal melanoma (Sheng et al, 2019). We summarized three clinical trial AEs to better describe the safety profile of anti–PD-1 therapy combined with antiangiogenic therapy
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