RTP On Demand — Head & Neck/Thyroid | Research To PracticeCase: A 73-year-old woman who experienced severe skin toxicity on a trial of vemurafenib
4:40 minutes.
TRANSCRIPTION:
DR COHEN: This was a 73-year-old woman who actually came to us from her medical oncologist who had been seeing her for some time, just a few months, but she clearly had progressive disease and, unfortunately, had some bulky disease in the chest that was producing symptoms. She had a cough. And he actually did mutational testing. DR LOVE: So she was RAI-insensitive at that point? DR COHEN: Right. She had received actually 3 courses of radioactive iodine, now was clearly growing, refractory to radioactive iodine. DR LOVE: And so she got BRAF testing. What was seen? DR COHEN: And she had the typical BRAF mutation, the V500E that, again, we see in different diseases and including about 50% of papillary thyroid cancer patients. It is associated with a more aggressive phenotype, so not surprising, perhaps, that her disease was behaving aggressively. And knowing that, he referred her to see us, because we had a clinical trial with vemurafenib. DR LOVE: We’ll talk about the data behind this, but I’m just kind of curious in general, putting trials aside. In a patient with a BRAF mutation, would you generally start with a BRAF inhibitor or a TKI? DR COHEN: I think outside of a clinical trial, given the Phase III data for TKIs and the fact that patients with BRAF mutations do appear to benefit — and that was true for the sorafenib and the lenvatinib study — I would start with a TKI. DR LOVE: So this lady, though, went on a trial of vemurafenib. And what happened? DR COHEN: That’s right. So she was treated with single-agent vemurafenib, and she had a dramatic response. Within 2 weeks, her cough was almost completely gone. Scanning confirmed that she indeed had a very nice clinical response. The other side of the coin was that she also suffered the typical skin manifestations, or skin side effects, of BRAF inhibitors, including vemurafenib. DR LOVE: What specifically happened? I know one thing that we hear a lot about in melanoma is skin sensitivity, sunburn. Did she have any of that? DR COHEN: She did. We advised her, of course, to stay out of the sun. So photosensitivity wasn’t necessarily such an issue, but she developed multiple papillomas in different areas and other erythematous lesions. We actually had her seeing a dermatologist on a regular basis. Many of these lesions need to be treated topically. They were very bothersome to her. In fact, we had to dose reduce her. We had to dose reduce her twice. And then the more serious manifestation, which she did have, was actually a squamous cell carcinoma that she developed on her leg. And that, of course, had to be excised. DR LOVE: What did it look like? Did it look any different than the other lesions? DR COHEN: It did. It was clearly ulcerating. It was growing at a faster pace. There was no doubt that this was a more serious lesion. DR LOVE: So how long was she on treatment? DR COHEN: So she was on treatment for just under a year. And she actually came off treatment because of the skin toxicity. DR LOVE: So at the time she came off treatment her tumor was under control? DR COHEN: It was still under control, and from a cancer perspective she was still doing well. But as I said, we had dose reduced her twice. And she was really suffering from the skin manifestations. And she said, “This isn’t worth it.” DR LOVE: So what was the next step? DR COHEN: Then we actually talked to the oncologist that had referred her, we maintained a very good relationship and communication and, at that point, it was a TKI. DR LOVE: What about the combination of BRAF inhibitors and MEK inhibitors, as is being done in melanoma? DR COHEN: As you know, the data for melanoma look strikingly good. And as we begin to understand the biology of BRAF mutation in melanoma, which I think should be the same biology in thyroid, we begin to realize why that combination works so well. Now, I think it’ll work in thyroid cancer as well. There are studies about to be initiated doing that, exactly, in fact, randomizing patients to a BRAF inhibitor versus the combination, similar to what was done in melanoma. And I would, in fact, be surprised if we didn’t see the same encouraging data as we’re seeing in melanoma. DR LOVE: I guess the other thing relevant to this patient is maybe it seems like with the combinations there are some toxicities that actually are less. Including the skin problems she had. DR COHEN: And especially the skin toxicity, because, of course, the agents are a little bit different, but with melanoma we’ve been able to back off a little bit on the doses in combination and get actually even superior efficacy. |