Transcript:Keith T. Flaherty, MD: Jonathan, we rely on you a little bit. For the occasional patient with metastatic basal cell carcinoma, we medical oncologists get involved and have used vismodegib and sonidegib, two new hedgehog inhibitors. But, there are vastly more patients out there with locally advanced disease, recognizing, of course, many basal cell patients are cured with available surgery and surgery alone. You’ve got radiation, even topical treatment. How do you see these agents influencing practice, and what do you define as a locally advanced type patient that you would think this would be a useful approach?

Jonathan S. Zager, MD: So, the same principles apply. As we discussed before, the first thing we look at is the cosmetic and the functional outcome if I were to resect it. The good thing about basal cell carcinomas, recurrent or multifocal, multiple basal cell, and basal cell nevus syndrome is that some of these patients can have Mohs surgery, which conserves tissue and then the cosmetic and functional outcome might be better. When the patient comes to me with a recurrent basal cell, that’s my first thought. What kind of cosmetic or functional defect is the patient going to have? If I think it’s appropriate for surgery, we’ll do surgery alone. We can also employ neoadjuvant strategies with the hedgehog inhibitors. We know that they’re not very durable. The progression will eventually happen maybe within a year, but as soon as the patient plateaus with their response, then we go ahead and we jump in with surgery. Again, these tumors are also somewhat radiosensitive, so radiation plays a role as well. Multi-modality therapy and multi-modality approach to the patients with recurrent basal cell carcinoma is best. I think surgery, radiation, and hedgehog inhibitors are the best approach.

Keith T. Flaherty, MD: When vismodegib was developed, it was pretty clear from the early studies, even the phase I studies, that the pharmacokinetics of the drug were unique in that it seemed like there wasn’t a real dose response relationship established. And so, what was brought forward was essentially a lower end of the dose range. It does have side effects that are bothersome to patients, this altered sense of taste.

Jonathan S. Zager, MD: And hair loss.

Keith T. Flaherty, MD: And with that, weight loss often times, and some fatigue, as well. So, the new kid on the block in this space is sonidegib. It was developed a little bit differently, a different drug in the sense that it’s a hedgehog inhibitor, but different properties. And in the randomized phase II study, it looked like there was similar efficacy, but clearly less toxicity with lower dose, which is ultimately what was introduced. Do you see that as an improvement in terms of just tolerability if you’re going to try to keep a patient on 6 months, 12 months on treatment?

Jonathan S. Zager, MD: Yes, absolutely. It’s definitely an improvement in terms of the toxicities. Again, another great drug for metastatic basal cell carcinoma that there’s really not much that surgeons are going to be able to do. These multifocal basal cell nevus syndrome patients, they’re not really surgical candidates except for the lesions that need palliation. But, for the neoadjuvant strategies, that’s also a great drug to use.

Keith T. Flaherty, MD: Great. Well, it’s exciting to see, even for that relatively small population, this really almost perfect correlation with these mutations and the disease. It goes back to CML where you almost don’t need to go looking for the genetic alteration. You can have confidence. This is the case, as well, where the molecular testing isn’t part of practice, right, you just assume.

Jonathan S. Zager, MD: Right, just give the drug, yes, exactly.

Keith T. Flaherty, MD: Right. Great. If anybody in the audience gets a chance to interact with their dermatologists and surgeon in the management of these patients, you can have reasonable confidence that this is a very trustworthy, if you will, oncogene targeted therapy.

This has been extremely informative. We’ve discussed several important scenarios in the treatment of melanoma and, just a moment ago, basal cell carcinoma. Before we end this discussion, I’d like to get final thoughts from each of our panelists. So, Dr. Long?

Georgina Long, BSc, MBBS, FRACP: Watch this space. Melanoma is an exciting cancer that’s really forging the way of treating cancer in a novel way. I’m here for a cure, and I’m really keen to continue to pursue that with clinical trials of novel combinations, because I would like to see the cure rate of melanoma increase. I think we are curing about one-third of patients. And I say that, use the C word, cure, but I’d like to do more. But, it’s an exciting, exciting time to be in cancer treatment managing people.

Keith T. Flaherty, MD: Dr. Luke?

Jason J. Luke, MD, FACP: Twelve FDA approvals in the last 5 years, I think several more that we’re all aware of coming very soon. I think the best is yet to come and can’t emphasize enough that we can’t make progress unless patients participate in clinical trials. We want higher efficacy, lower toxicity, and it’s there. We can get there.

Keith T. Flaherty, MD: Dr. Weber?

Jeffrey S. Weber, MD: I certainly agree with what my colleagues have said. I think one important point is there’s an amazing amount of information to be mined from the existing databases of thousands of patients who have received a combination targeted therapy, single agent immunotherapy, or combination immunotherapy. And I would certainly urge the sponsors who have a hold of those data to allow investigators to mine those databases.

Keith T. Flaherty, MD: Great. Dr. Zager?

Jonathan S. Zager, MD: I agree with everybody. I think multi-modality, multi-discipline approach to melanoma, especially surgery, as you guys start to really get great responses will play a role in later stages, more so than it has in the past. And I think that we’re really making great advances.

Keith T. Flaherty, MD: Absolutely. Well, thanks to all of you for your contributions to this discussion. On behalf of our panel, we thank you for joining us, and we hope you found this peer exchange discussion to be useful and informative.

Transcript Edited for Clarity