Apatinib Prompts Responses in Patients With Recurrent Melanoma

Apatinib (Rivoceranib) may be a suitable second-line treatment option for a subset of patients with recurrent or refractory melanoma, according to a new report.

Molecular-targeted therapy and immunotherapy have dramatically changed the treatment of patients with advanced melanoma in recent years, noted corresponding author Quanli Gao, MD, PhD, of the Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, in China. BRAF and MEK inhibitors, as well as immune checkpoint inhibitors, have led to promising results and extended progression-free survival (PFS), Gao and colleagues said. Yet, not all patients respond to these therapies, and in such cases, there is no recommended treatment option.

Writing in the journal The Oncologist, the investigators said new therapeutic options are needed to fill the gap in effective treatments. They noted that in China, the most common types of melanoma—acral and mucosal melanoma—often lack mutations of BRAF, RAS, and NF1, rendering them less susceptible to many of the currently available therapies.

Gao and colleagues suspected that apatinib, an oral, small-molecule vascular endothelial growth factor receptor-2 (VEGFR-2) inhibitor, might be a good option for certain patients with refractory melanoma, noting that it has led to results against several different cancer types, but has not been extensively studied in melanoma.

The investigators identified 15 patients with advanced melanoma who experienced a recurrence following at least one first-line therapy. Two of the patients had V660E BRAF mutations, 2 had an unknown mutation status, and the remaining 11 had wild-type V660E BRAF. Patients were administered daily 500 mg doses of apatinib. The primary endpoint was PFS, and secondary endpoints were objective response rate (ORR), disease control rate (DCR), and overall survival (OS).

The therapy yielded a partial response in 2 patients, for an ORR of 13.3%. No patients experienced a complete response. Eleven patients had stable disease following therapy (DCR: 86.7%), and 2 patients had progressive disease. Patients in the study had a median overall survival of 12.0 months, the investigators reported.

“Although apparently not as effective as BRAF and MEK inhibitors, considering that the patients enrolled are on at least second-line treatment, apatinib has shown an efficacy signal and is worthy of large-scale clinical studies in malignant melanoma,” Gao and colleagues concluded.

In terms of adverse events, the most common treatment-related adverse event was hypertension (80%), followed by oral mucositis (33.3%) and hand-foot skin reactions (26.7%), the authors said. Liver function abnormalities, hemorrhage, and diarrhea were also reported. Only 2 patients experienced grade 3 or above treatment-related adverse events. One patient had grade 3 hypertension, and one patient had grade 4 oral ulceration. No patients died as a result of treatment.

Gao and colleagues noted that when they began recruiting patients for the study, they initially targeted patients who had only been treated with dacarbazine-based chemotherapy, which was the standard first-line therapy. However, over the course of recruitment, vemurafenib (Zelboraf) and PD-1 monoclonal antibodies were approved, which made it difficult to identify patients who had received only the first-line treatment. At that point, the study’s parameters were revised to include patients who had already undergone second-line treatment. In the end, 9 of the 15 patients had just first-line therapy before apatinib, and the remaining 6 had had second-line therapy or above prior to enrollment.

Other limitations noted in the study were the small sample size and the homogeneity of the study population, since all patients enrolled were from China. Still, the investigators said the data support the idea that apatinib can achieve anti-tumor activity in patients with metastatic melanoma in a second-line setting or beyond.

Reference

Yuan S, Fu Q, Zhao L, et al. Efficacy and safety of apatinib in patients with recurrent or refractory melanoma. Oncologist. Published online March 28, 2022;. doi:10.1093/oncolo/oyab068