Camrelizumab Plus Apatinib and Temozolomide as First-Line Treatment in Patients With Advanced Acral Melanoma

Abstract

ImportanceAcral melanoma, known for low tumor mutation burden, responds poorly to immunotherapy. A standard therapy is still lacking.ObjectiveTo investigate the activity and safety of camrelizumab (an anti–programmed cell death-1 antibody) plus apatinib (a vascular endothelial growth factor receptor 2 inhibitor) and temozolomide as first-line treatment in patients with advanced acral melanoma.Design, Setting, and ParticipantsIn this single-arm, single-center, phase 2 nonrandomized clinical trial, patients with treatment-naive unresectable stage III or IV acral melanoma were enrolled at Peking University Cancer Hospital and Institute between June 4, 2020, and August 24, 2021. The data cutoff date was April 10, 2022.InterventionsPatients received 4-week cycles of intravenous camrelizumab, 200 mg, every 2 weeks; oral apatinib 250 mg, once daily; and intravenous temozolomide, 200 mg/m2, once daily on days 1 to 5 until disease progression or unacceptable toxic effects.Main Outcomes and MeasuresThe primary end point was objective response rate as assessed by investigators according to the Response Evaluation Criteria In Solid Tumors (version 1.1). Secondary end points included progression-free survival, time to response, duration of response, disease control rate, overall survival, and safety.ResultsA total of 50 patients (32 men [64%]; median age, 57 years [IQR, 52-62 years]) were enrolled and received treatment. The median follow-up duration was 13.4 months (IQR, 9.6-16.2 months). The objective response rate was 64.0% (32 of 50; 95% CI, 49.2%-77.1%). The median time to response and duration of response were 2.7 months (IQR, 0.9-2.9 months) and 17.5 months (95% CI, 12.0 to not reached), respectively. The disease control rate was 88.0% (44 of 50; 95% CI, 75.7%-95.5%). The estimated median progression-free survival was 18.4 months (95% CI, 10.6 to not reached). The median overall survival was not reached. The most common grade 3 or 4 treatment-related adverse events were increased gamma-glutamyltransferase levels (15 [30%]), decreased neutrophil count (11 [22%]), increased conjugated bilirubin levels (10 [20%]), and increased aspartate aminotransferase levels (10 [20%]). No treatment-related deaths occurred.Conclusions and RelevanceThe findings of this nonrandomized clinical trial suggest that camrelizumab plus apatinib and temozolomide may be a potential first-line treatment option for patients with advanced acral melanoma, which warrants further validation in a randomized clinical trial.Trial RegistrationClinicalTrials.gov Identifier: NCT04397770

Management of acral lentiginous melanoma: current updates and future directions

“…studied combination therapy with camrelizumab, apatinib, and temozolomide as first-line therapy for 50 patients with ALM. This study found a particularly high ORR of 64%, median PFS of 18.4 months, DCR of 88%, median time to response of 2.7 months, and median duration of response of 17.5 months ( 58 ). A similar recent prospective phase II study by Wang et al., also out of China, studied 30 patients with ALM treated with first-line combination therapy with apatinib and camrelizumab.…”

“…Other combinations including medications such as camrelizumab, apatinib, and temozolomide have also shown promising results ( 58 , 59 ). A prospective study treating patients with a combination of camrelizumab, apatinib, and temozolomide found a particularly high ORR of 64% and DCR of 88% ( 58 ). A similar DCR was found in a study using a regimen of apatinib and camrelizumab, but the ORR was found to be lower, at 24.1% ( 59 ).…”

“…In general, ALM seems to respond to anti-PD1 therapy, more specifically with combination therapy regimens, typically including anti-PD1 therapy with anti-CTLA4 therapy ( 49 , 50 , 52 , 53 , 55 – 57 , 60 – 62 ). Other combinations including medications such as camrelizumab, apatinib, and temozolomide have also showed particularly promising results, but need further analysis ( 58 , 59 ). Patients with BRAF V600E-mutant ALM might be good candidates for targeted BRAF inhibitor therapy, although more studies are needed to support this ( 63 – 65 ).…”