Objective Treatment for advanced melanoma after progression on immunotherapy is limited. This phase II trial (NCT03422445) was conducted to evaluate the efficacy and safety of apatinib plus temozolomide in patients with advanced melanoma after failure of immunotherapy. Methods Patients with unresectable stage III or stage IV melanoma after progression on immunotherapy were treated with temozolomide 300 mg on days 1–5 and apatinib 500 mg daily every 28-day cycle until disease progression or intolerable toxicities. Besides immunotherapy, prior chemotherapy, targeted therapy, and clinical trials were allowed. The primary endpoint was progression-free survival. Secondary endpoints were objective response rate, disease control rate, overall survival, and safety. Results Of 29 patients, 28 (96.6%) had metastatic diseases, and the predominant subtypes were mucosal [12 (41.4%)] and acral melanoma [eight (27.6%)]. Five (17.2%) patients showed BRAF, CKIT, or NRAS mutation. Five achieved confirmed partial response, with an objective response rate of 17.2%. The disease control rate was 82.8%. The median progression-free survival was 5.0 months [95% confidence interval (CI): 4.7–5.3], and the median overall survival was 10.1 months (95% CI: 5.1–15.0). Grade 3–4 treatment-related adverse events included proteinuria [four (13.8%)], thrombocytopenia [two (6.9%)], hypertension [one (3.4%)], and hyperbilirubinemia [one (3.4%)]. No treatment-related death occurred. Conclusion Apatinib plus temozolomide demonstrated promising efficacy and manageable safety profile in patients with advanced melanoma after progression on immunotherapy. * Li Zhou and Yue Yang contributed equally to the writing of this article and are the co-first authors. Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website, www.melanomaresearch.com. Received 11 November 2021 Accepted 25 January 2022 Correspondence to Chuanliang Cui, Department of Renal Cancer and Melanoma, Peking University Cancer Hospital and Institute, Beijing, China, Tel: +8610 88196317 -mail: 1008ccl@163.com Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.
