Question: The ipilimumab trial paired ipilimumab with dacarbazine. Is DTIC still an option?
Dr. Wolchok: Looking at the result as someone who has been taking care of patients with melanoma using ipilimumab for several years, I think it is still unknown whether dacarbazine should be added. My own opinion would be to oncologists in the community that if they are going to give ipilimumab at 3 mg/kg to stick with the monotherapy label because we really don’t have data comparing ipilimumab with dacarbazine alone at that dose. And so I think we stick with what we know produces an overall survival benefit.
There are reasons to imagine the addition of dacarbazine could make results better by killing some cancer cells and releasing some antigenic debris that would serve as a target for the immune system. Chemotherapy can also be thought of as changing the tumor microenvironment, which might be advantageous, but chemotherapy could also be immunosuppressive. So we could really make a case either way that dacarbazine added to or detracted from or left things just the same.
Question: Will interleukin-2 still have a role in melanoma treatment?
Dr. Sondak: I am still going to use IL-2, and it makes the most sense if you have someone who uses IL-2 most of time, you will want to use that first before you use anything else. Why? Ipilimumab is tough on the patient. We want them in as good shape as possible. ... We know if they get IL-2 first and then get ipilimumab; the results are just as good, if not better. We don’t know the opposite way. And we also know that a lot of people on ipilimumab get side effects. They wind up on steroids and other immunosuppressive drugs that would make it very difficult to put them on IL-2.
Vemurafenib is going to change a lot of things. A lot of people are too far gone to have surgery, too far gone to have IL-2. Now we have BRAF mutant melanoma [patients] who will get vemurafenib, and shrink down... If we could keep a close eye and figure out when is right time, we are going to do more surgery and maybe IL-2 in those patients because we are going to restore them to place where IL-2 is going to have more room to work. But it’s not going to be 80% of people getting IL-2. It is going to be a very restricted group of people treated by a very specialized group of doctors.
Dr. Eggermont: I think IL-2 will move down in the options list. IL-2 will remain as an option in second or third line, and IL-2 will also be an option in combination with ipilimumab because [Dr.] Steve Rosenberg already did a trial in 36 patients ... and the majority of the complete responders are alive 6 years and longer and are still in complete remission (ASCO 2010, Abstract 8544). The combination of IL-2 and ipilimumab will be relaunched, I am sure.
Question: And interferon – Where will it fit in?
Dr. Sondak: We don’t know how long we should treat people, how intensively, and how we should combine the new and the old, and the data that we have just doesn’t sort it out. On the other hand, if you look at the whole landscape, it actually makes adjuvant treatment with interferon more important now than it used to be.
It’s very clear that interferon treatment does delay recurrences in a substantial fraction of patients. It may not cure many people, but it delays recurrence in quite a few people, and right now today we are so much better off than we were in melanoma 2 years ago and I have no doubt that 2 years from now just with stuff we heard about at this meeting we will be much more clear on how do we use how do we take care of side effects not to mention other new exciting drugs that we hope 2 years from now will start to be available.
In the past we debated, does it even matter that we delay recurrence. The ASCO answer should be, "It absolutely matters to our patients." So interferon and any form of adjuvant therapy is suddenly a bridge. It is a shaky bridge – made with some ropes and a few planks – it isn’t very sturdy to walk on, but we’re trying to get from here, one place where it was safe to another place where hopefully we are better off and not at the bottom of ravine. It’s real exciting – not just the data we already have but for the future and how many patients this will affect positively.