Immunomodulatory antibodies for melanoma treatment prove promising

July 1, 2011

Novel immunomodulatory antibodies such as ipilimumab (Bristol-Myers Squibb) and other experimental treatment options such as melanoma vaccines, chemotherapy agents (Abraxane, Celgene) and targeted drug therapies (BRAF inhibitors) are proving effective in the treatment of patients with late-stage melanoma, offering increased hope in the continuing battle against this deadly skin cancer.

Key Points

Tampa, Fla. - Novel immunomodulatory antibodies such as ipilimumab (Bristol-Myers Squibb) and other experimental treatment options such as melanoma vaccines, chemotherapy agents (Abraxane, Celgene) and targeted drug therapies (BRAF inhibitors) are proving effective in the treatment of patients with late-stage melanoma, offering increased hope in the continuing battle against this deadly skin cancer.

Ipilimumab advancement

The preliminary results that have been made public in the ongoing randomized clinical trial with ipilimumab in untreated stage 4 melanoma patients seem to be very promising, Dr. Weber says. Trial participants either received both dacarbazine and ipilimumab or dacarbazine alone as a monotherapy.

According to Dr. Weber, one would expect a 10-month median survival in those patients receiving dacarbazine alone and slightly better outcomes in those patients receiving ipilimumab alone. The preliminary trial results indicate, however, that patients who received both ipilimumab and dacarbazine do better, with the trial meeting its endpoint of prolonged survival, compared to those who received dacarbazine alone.

Moreover, a survival advantage was seen in previously treated patients who received ipilimumab in another phase 3 trial, and in that trial benefit was also achieved in those patients who had melanoma metastases involving the brain.

"This is an important advance, as the novel combination of dacarbazine and ipilimumab may represent a new standard of care in melanoma patients. However, the final results of the trial will elucidate the true utility of this treatment approach," Dr. Weber says.

One could argue that ipilimumab is the agent that is more responsible for the positive outcomes seen in the trial. However, preliminary trial assessments indicate that both of these drugs complement each other in the treatment of late-stage melanoma.

Progressive success

According to Dr. Weber, it is possible that the anti-tumor responses evolve over time in certain patients treated with ipilimumab. Therefore, the lack of initial clinical response does not necessarily translate into treatment failure, as the onset of a response may follow progressive disease or stable disease. Nevertheless, targeting CTLA-4 with immunomodulatory antibodies such as ipilimumab appears to benefit a subset of patients with metastatic melanoma.

Ipilimumab may also be used in combination with other evolving therapies such as peptide-based melanoma vaccines or more targeted drugs such as BRAF inhibitors. Though many of the experimental treatment approaches have shown efficacy in the treatment of melanoma to a greater or lesser degree, there is no hierarchy among them, as some agents may have a greater efficacy in different subsets of patients.

The BRAF inhibitor PLX4032 may receive approval by the Food and Drug Administration (FDA) soon, and ipilimumab was approved by the FDA at the end of March, Dr. Weber says. Patients who are BRAF-mutated will likely receive this treatment as a first-line therapy. Should they fail BRAF inhibitor therapy, ipilimumab would likely be the next best therapeutic option. Patients who are BRAF wild-type would likely first receive ipilimumab, however.

"I think you will find that melanoma patients will do better in this decade than the decade before. Several new and exciting treatment options will soon be available to our melanoma patients, some of which can significantly improve outcome compared to years ago," Dr. Weber says.

Disclosures: Dr. Weber has consulted for and has received honorarium from Bristol-Myers Squibb and Pfizer, as well as for Roche and GlaxoSmithKline, companies that make some of the BRAF inhibitors.