Oral agent for metastatic melanoma maintains promising activity in trial

March 1, 2011

Results from a multicenter phase 2 open-label study corroborate promising outcomes of a phase 1 trial showing the oncogene-targeted oral agent RG7204 as a promising treatment for metastatic melanoma (MM). Also known as PLX4032, RG7204 is being codeveloped by Genentech and Plexxikon. It acts to selectively inhibit oncogenic BRAF, a serine-threonine protein kinase that has been implicated in the pathogenesis of melanoma.

Key Points

Denver - Results from a multicenter phase 2 open-label study corroborate promising outcomes of a phase 1 trial showing the oncogene-targeted oral agent RG7204 as a promising treatment for metastatic melanoma (MM).

Also known as PLX4032, RG7204 is being codeveloped by Genentech and Plexxikon. It acts to selectively inhibit oncogenic BRAF, a serine-threonine protein kinase that has been implicated in the pathogenesis of melanoma. A specific mutation, V600E, is the most common BRAF mutation and has been identified in more than 50 percent of melanomas in some studies.

Study details

Best overall response rate assessed by an independent review committee using RECIST criteria was evaluated as the primary endpoint. After a median follow-up of about seven months, 52 percent of patients were categorized as responders based on a decrease in tumor size of at least 30 percent, and another 30 percent of patients had stable disease. Secondary endpoint analyses showed median progression-free survival was 6.2 months, median overall survival had not yet been reached and median duration of response was 6.8 months.

"So far, RG7204 appears to be a major step forward in the treatment of metastatic melanoma considering the limited benefit of dacarbazine (DTIC-Dome, Bayer). However, enthusiasm over the relatively high response rate for RG7204 must be tempered by the short duration of response, as 56 percent of patients discontinued treatment because of disease progression during a median follow-up of seven months," he says. "Hopefully, future research will identify combination regimens, perhaps using another targeted therapy or immunotherapy, that will prolong the benefit achieved."

In BRIM2, grade 3 or greater adverse events occurring at rates of 10 percent or higher included abnormal liver function (14 percent), joint pain/arthritis (11 percent) and gastrointestinal disorders, especially dysphagia and pancreatitis (10 percent). Overall, about 60 percent of patients developed joint pain. Other adverse events included rash, photosensitivity and hair loss. A grade 3 cutaneous squamous cell carcinoma (cSCC, keratoacanthoma subtype) developed in 34 (26 percent) of patients.

"RG7204 is associated with extreme photosensitivity so that patients must be very careful about sun exposure, and dermatologic monitoring for cSCC is also important," Dr. Lewis says. "However, patients who developed cSCC underwent excision of the lesion and continued treatment, and only four (3 percent) patients withdrew from the study because of an adverse event."

Disclosures: Dr. Lewis reports no relevant financial interests.