FDA Approves Liver-Directed Treatment for Adults With Metastatic Uveal Melanoma
The FDA approved the use of melphalan via a hepatic delivery system as a liver-directed treatment for adults with uveal melanoma with unresectable hepatic metastases that affects less than 50% of the liver and no extrahepatic disease. The approval also pertains to adults with uveal melanoma and extrahepatic disease limited to the bone, lymph nodes, subcutaneous tissues, or lung that is responsive to resection or radiation.
Metastatic uveal melanoma is a rare but aggressive metastatic cancer in which approximately 90% of cases involve the liver. Melphalan—a chemotherapy drug commonly used to treat multiple myeloma—is administered via an accompanying hepatic delivery system by infusion into the hepatic artery every 6 to 8 weeks for up to six total infusions. A recommended melphalan dose of 3 mg/kg is based on body weight, with a maximum dose of 220 mg during a single treatment.
The FDA approval follows the FOCUS study—a single-arm, multicenter, open-label trial in 91 patients with uveal melanoma with unresectable hepatic metastases. The study’s primary endpoint was objective response rate (ORR) and duration of response (DoR) as assessed by an independent central review committee using RECIST v1.1.
According to the results of the study, the ORR was 36.3% (95% CI: 26.4, 47) and median DoR was 14 months (95% CI: 8.3, 17.7).
The prescribing information has a Boxed Warning for severe peri-procedural complications including hemorrhage, hepatocellular injury, and thromboembolic events, as well as for myelosuppression with resulting severe infection, bleeding, or symptomatic anemia.
Because of this, the melphalan/hepatic delivery system is available only through a restricted program under a Risk Evaluation and Mitigation Strategy.
According to the FDA press release, “the most common adverse reactions or laboratory abnormalities were thrombocytopenia, fatigue, anemia, nausea, musculoskeletal pain, leukopenia, abdominal pain, neutropenia, vomiting, increased alanine aminotransferase, prolonged activated partial thromboplastin time, increased aspartate aminotransferase increased blood alkaline phosphatase, and dyspnea.”
Additionally, the treatment is contraindicated in patients with active intracranial metastases or brain lesions with a propensity to bleed, those with liver failure or a medical treatment of the liver in the previous 4 weeks, patient with cardiovascular conditions, and those with a history of allergies or known hypersensitivity to melphalan or the melphalan/hepatic delivery system, and more.
FDA approves melphalan as a liver-directed treatment for uveal melanoma. News release. US Food and Drug Administration; August 14, 2023. Accessed September 5, 2023. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-melphalan-liver-directed-treatment-uveal-melanoma