apatinib and Skin-Neoplasms

At present, immune monotherapy and combination therapy has not shown satisfactory effects on acral melanoma, and still no standard treatment is available for advanced acral melanoma. Here, a phase II trial was performed to explore the safety and efficacy of apatinib combined with camrelizumab in advanced acral melanoma patients as first-line therapy (NCT03955354).. Patients with pathologically confirmed, locally unresectable or metastatic treatment native acral melanoma received 250 mg apatinib once daily and camrelizumab 200 mg once every two weeks intravenously every 28-day cycle. The primary end-point was objective response rate and the secondary end-points were disease control rate, overall survival, progression-free survival and safety.. Thirty patients were recruited between January 2015 and January 2022. Among them, 21 (70.0%) had stage IV, and a median tumour burden was 50 mm (range: 11-187). Objective response rate was 24.1%, and 7 of 29 patients had an anti-tumour response, including partial response (n = 5) and complete response (n = 2). Disease control rate was 82.8%, median progression-free survival was 7.39 months (confidence interval: 3.65-9.92), and median overall survival was 13.4 months (confidence interval: 1.9-25.0). Grade 3-4 treatment-related toxicity (grade 3 50.5%; grade 4 3.3%) included transaminase elevations, proteinuria, leukocytopenia, vomiting, diarrhea and drug-induced liver injury. No treatment-related mortality occurred. The mutations of TTN, MUC16, VPS13D, ALPK2 and SCUBE1 showed significant alterations with survival outcome.. Apatinib combined with camrelizumab showed manageable safety profile and reasonable anti-tumour activity in advanced acral melanoma patients as first-line therapy.

Topics: Calcium-Binding Proteins; Humans; Melanoma; Melanoma, Cutaneous Malignant; Protein Kinases; Proteins; Skin Neoplasms

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. 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. 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. Apatinib plus temozolomide demonstrated promising efficacy and manageable safety profile in patients with advanced melanoma after progression on immunotherapy.

Topics: Antineoplastic Combined Chemotherapy Protocols; Humans; Immunotherapy; Melanoma; Pyridines; Skin Neoplasms; Temozolomide

Metastatic or relapsed angiosarcoma has a poor prognosis and the efficacy of conventional chemotherapy is often limited. Apatinib, a novel tyrosine kinase inhibitor (TKI) targeting vascular endothelial growth factor receptor-2 (VEGFR2), has been approved for the treatment of advanced gastric cancer.. Herein, we report a patient with advanced angiosarcoma, who received apatinib at a daily dose of 250 to 725 mg, resulting in a partial response for three months, which may be related to Kinase Insert Domain Receptor (KDR) gene amplification.. Our experience reported here indicated that apatinib may be a useful therapeutic option for treatment of patients with advanced angiosarcoma.

Topics: Aged; Antineoplastic Agents; Gene Amplification; Head and Neck Neoplasms; Hemangiosarcoma; Humans; Male; Neoplasm Metastasis; Neoplasm Recurrence, Local; Proto-Oncogene Proteins c-kit; Pyridines; Scalp; Skin Neoplasms; Vascular Endothelial Growth Factor Receptor-2

The effect of apatinib on the formation of vasculogenic mimicry (VM) was studied in a malignant melanoma cell line. MUM-2B cells cultured in three-dimensional Matrigel were treated with varying concentrations (0, 0.01, 0.05, 0.1, 0.5 μmol/L) of apatinib to test its effect on VM in vitro, followed by MTT proliferation and transwell invasion assays to determine the effect of apatinib on cell proliferation and invasion of MUM-2B cells. In vivo, we used a melanoma cancer model to test the effect of short-term apatinib (100, 200, 300 mg/kg) treatment on VM. Western blotting, immunohistochemistry staining, and CD31-PAS dual staining were performed to assess the expression of VEGFR-2, ERK-1/2, PI3K, and MMP-2, and formation of VM. The results showed apatinib-treated groups formed a lesser number of VM in 3D matrigel, while the cell viability in MTT proliferation assay and the number of migration cells in transwell invasion assay were significantly lower in apatinib-treated groups. In addition, short-term apatinib treatment inhibited angiogenesis, VM formation, and tumor growth in models of melanoma cancer. Mice in apatinib-treated groups showed a markedly reduced expression of VEGFR-2, ERK-1/2, PI3K, and MMP-2. In summary, apatinib could inhibit the expression of VEGFR-2, and downregulate the ERK1/2/PI3K/MMP-2 signaling cascade, which may be one of the underlying mechanisms by which apatinib inhibits angiogenesis and the development of VM in models of melanoma cancer, and restrains the formation of VM by MUM-2B cells. Apatinib shows inhibitory effects on cell proliferation and invasion of MUM-2B cells, which is a close relationship with the VM.

Topics: Animals; Antineoplastic Agents; Binding Sites; Cell Culture Techniques; Cell Line, Tumor; Cell Movement; Cell Proliferation; Cell Survival; Drug Screening Assays, Antitumor; Extracellular Signal-Regulated MAP Kinases; Female; Humans; Matrix Metalloproteinase 2; Melanoma; Mice; Mice, Inbred BALB C; Neoplasm Invasiveness; Neoplasm Transplantation; Neovascularization, Pathologic; Phosphatidylinositol 3-Kinases; Pyridines; Signal Transduction; Skin Neoplasms; Vascular Endothelial Growth Factor Receptor-2