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Richard Joseph, MD, is an assistant professor of medicine/oncology at Mayo Clinic. His Hematology/Oncology fellowship was completed at MD Anderson Cancer Center. He is a voting member of the NCCN (National Comprehensive Cancer Network. He belongs to Melanoma International’s Scientific Advisory Board and received MIF’s Doctor of the Year award for 2015.


» DRUG HOLIDAY
I would like to know what we know about the rumored drug holiday for BRAF inhibitors, is this proven to get a better response?

Dr. Joseph: “In animals, intermittent administration did appear to be helpful in delaying resistance to BRAF inhibitors which subsequently led to a trial in humans. At this point, this strategy remains investigational as the trial is not complete. I do have experience with patients receiving benefit to BRAF inhibitors after restarting them after a break. The question remains is whether the patients are receiving better or worse benefit than if they remained on the drug.”

» IPI/ANTI-PD1 COMBINATION
If you had ipi followed quickly by antipd1 would that have the same effect as the combo but fewer side effects?

Dr. Joseph: “This is a good question that at this point is impossible to answer definitively. In the initial phase 1 study combining ipilimumab and nivolumab, there was an arm of patients who received ipilimumab first followed by nivolumab in sequence rather than together at the same time. This arm appeared to have a less efficacy than the combination arms which is why BMS decided to move forward with the combination rather than sequential therapy.”

» OCULAR/MUCOSAL MELANOMA
Now that IPI and the PD1’s are around for a while and have accumulated many hundreds of patients, has there been any data, studies done or any other indications that differentiates ocular and mucosal melanomas response rates to those meds from that of cutaneous melanoma?

Dr. Joseph: “Another great question. For mucosal melanoma, the response rate to immunotherapy appears to be similar but perhaps slightly less than cutaneous melanoma. There will be more data presented on this topic in the coming months. For ocular melanoma, there is less data as these patients were excluded from a lot of the larger trials. Mayo Clinic did present an abstract at ASCO 2015 with 7 patients with ocular melanoma who received pembrolizumab on the expanded access program and the response rate was similar to what you would expect with cutaneous melanoma. The sample size of course is very small so it is hard to extrapolate. There are current and future studies designed to answer these questions.”

» NIVO/KEYTRUDA RESPONSE
Have there been patients not responding to nivo that did respond to keytruda or vice versa?

Dr. Joseph: “I am not aware of this happening.”

» VACCINE
My 2000 Stage IV melanoma metastasized and returned in 2003/2004 (intestines and lymphatic system). I participated in a clinical trial (a vaccine/autologous program that used one of my tumors and white blood cells …) that was administered to me one time on each of 3 consecutive months during the summer of 2004. I was one of eighteen participants in the trial. Sadly, all of the remaining trial participants succumbed to their melanoma within a year after the trial concluded. My question to you is this; since the vaccine worked on/for me why has my “success” not been of any interest to those of you in the medical and medical research field. There is much to be learned here. I am so disappointed that there has been no interest what-so-ever from those of you involved the melanoma research/treatment field.

Dr. Joseph: “This is a remarkable story and I’m truly happy for you. I’m sure your success is of great interest to many researchers, however, there are multiple challenges when studying an individual case.”

» TAFINLAR/MEKINIST
My father has been taking Tafinlar 100 mg BID for 7 months now. His tumor had the BRAF gene. So far he has been tolerating the drug well and his brain met has disappeared. No new lesions. So this is great news. His doctor is holding off on the MEK drug at this time until she feels “she needs to add it.” Recently, he has become anemic with some weight loss secondary to decreased appetite and experiencing increased fatigue. How long should he continue on the tafinlar?

Dr. Joseph: “Recently, the combination of tafinlar/mekinist has demonstrated a significant improvement in not only progression free survival but also overall survival. Given the improvement in overall survival, I tend to use the combination rather than the single agent. With that being said, the combination is a bit more toxic than the single agent and in patients who are especially frail, I might tend to only give the BRAF inhibitor instead of the combination. I would discuss the rationale of holding mekinist further with your father’s treating physician.”

Do you have a question you would like to have considered for the next column? Email cpoole@melanomainternational.org.

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