Can Adding Bevacizumab Improve Outcomes in Mucosal Melanoma?

CHICAGO-A combination regimen of bevacizumab, a blood vessel growth inhibitor, with carboplatin plus paclitaxel appears to be active and safe as first-line treatment in patients with advanced mucosal melanoma, according to the results of a phase II trial (abstract 9521) presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting, held May 31–June 4 in Chicago.

“There is not standard treatment for mucosal melanoma, and though we give chemo for first-line treatment, the response rate is less than 10%,” said corresponding author of the study, Jun Guo, MD, of the Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) in the Department of Renal Cancer and Melanoma at Peking University Cancer Hospital & Institute in Beijing.

While mucosal melanoma is not common in Caucasian populations, it is the second most common subtype of melanoma in Asians. Since these tumors tend to be highly vascularized, the investigators reasoned that adding bevacizumab may make chemotherapy more effective in this patient population.

The study was an open-label, multicenter, randomized phase II trial of patients with metastatic, recurrent, or unresectable mucosal melanoma, who had not received previous systemic therapy. Between 2014 and 2017, patients were randomized 2:1 to receive bevacizumab 5 mg/kg every 2 weeks or placebo with carboplatin AUC 5 plus paclitaxel 175 mg/m². Treatment was continued until disease progression, unacceptable toxicity, death, or withdrawal of consent. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival, disease control rate, and safety.

Of the 114 total patients, 76 patients were assigned to the bevacizumab arm and 38 to the placebo arm. On average, patients received 4 and 3 treatment cycles in the bevacizumab and placebo groups, respectively; 21.1% and 13.2% received 5 or more cycles. The median PFS was 4.7 months for the bevacizumab arm and 3.2 months for the control arm (hazard ratio [HR], 0.50; 95% CI, 0.33–0.72; P = .001). The median OS was 13.7 months (range, 11.1–15.6 months) in the bevacizumab arm vs 9.1 months (range, 8.0–14.0 months) in the placebo arm (HR, 0.61; 95% CI, 0.40–0.91; P = .016).

“Ultimately, it didn’t meet its primary endpoint of a 3-year improvement of PFS,” said Sophie Neumann of Institut Curie in Paris, who was the discussant for the study.

The incidence of grade 3/4 adverse events was 42.1% in the bevacizumab arm and 34.2% in the placebo arm. No additional toxicities were reported in the bevacizumab arm relative to the placebo arm.

“My main comment is-is this combo still relevant in 2019 for mucosal melanoma patients?” concluded Neumann.