Unmet Needs and Future Treatments of Metastatic Melanoma
Insights From: Adil Daud, MD, University of California Medical Center
The big problem in melanoma continues to be the fact that resistance develops so often to these treatments. And for the BRAF and MEK inhibitors, although these long-term data are reassuring, we know that patients who have complete responses, who don’t have LDH [lactate dehydrogenase] elevations, who are on limited types of diseases will do well. Many of our patients have extensive sites of disease, many of patients have elevated LDH, many of our patients will not have a complete response. So where do we go with those folks?
I think the 1 interesting direction is the combination where immunotherapy and BRAF/MEK inhibitors are combined altogether, where there have been 3 trials. Most of them have been small, showing some benefit in terms of combining all 3, and there are some large, randomized phase III trials ongoing to look and see whether that benefit is prolonged and that benefit is statistically and clinically significant.
I think other interesting directions that people are going in are looking at different drugs, looking at drugs like ERK inhibitors, looking at PI3 kinase inhibitors, where people think that those might be able to face all resistance or might hold off resistance. And it’s possible that some of these combinations might help us get better responses. People are looking at different BRAF inhibitors and different MEK inhibitors, which might be able to have a different spectrum of adverse effects. You know, if somebody has really bad adverse effects of 1 type, like skin rash. Like there are patients for whom the skin rash is really bad. Like it could be Stevens-Johnson syndrome or TEN, toxic epidermal necrolysis. I just had a patient who had 1 of these types of rashes, then had an episode of fever and chills, and then had a toxic skin reaction. Probably in the case of this patient, we probably will switch him to a different BRAF/MEK inhibitor combination where presumably he doesn’t share something like an allergy or a hypersensitivity reaction to these exact drugs.
I think there are a lot of exciting directions going on. In colon cancer, which is different from melanoma, it appears that combining EGFR blockade to BRAF and MEK inhibitors can give you some mileage over just chemotherapy and EGFR inhibitor combinations. I think that’s something that we could learn from melanoma.