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What’s Next After Hedgehog Therapy Fails for Basal Cell Carcinoma?

CURECURE® Winter 2021

A patient with recurrent basal cell carcinoma discusses his cancer journey, his latest challenge and how he’s now prioritized quality of life over quantity.

Basal cell carcinoma (BCC) is the most common type of skin cancer, with approximately 8 in 10 skin cancers being BCC. This type of cancer originates in the lower part of the epidermis in sun-exposed areas such as the head, neck and face. It typically grows slowly, but if left untreated, can progress to other areas of the body in addition to the bone.

This form of skin cancer is associated with disturbances in hedgehog signaling, which involves certain cells and is critical for skin repair. Hedgehog pathway inhibitors have recently been approved as first-line therapy for patients with advanced BCC and other difficult-to-treat scenarios. Although this novel class of inhibitors has been shown to be safe and effective for locally advanced BCC and metastatic BCC, it may not be the right fit for every patient.

CURE® spoke with Jeffrey Wittig, a 62-year-old patient with recurrent BCC who has had skin cancer in one form or another since his 40s. He was treated with hedgehog therapy for BCC, which is now creeping toward his brain. Despite this outcome, he emphasizes the importance of perseverance throughout this process.

Q: CURE®: Can you tell us how your journey with BCC began?

A: Wittig: It began a number of years ago, probably more than 15, with small things that were scraped and burned, and (it got) progressively worse to the point where major things were being removed — large skin grafts, forehead flap. I had radiation in 2012 on the bone in my nose because the BCC had spread to the bone. And then from 2012 to now, (it got) progressively worse to the point that I had a partial rhinectomy four years ago and then a complete rhinectomy three years ago. I had my nose reconstructed at Dana-Farber (Cancer Institute). I guess that would tell you how bad it’s gotten and what the journey has been.

Q: When you were originally diagnosed with BCC, at what stage were you diagnosed?

A: I’ve had 41 surgeries, so you’d have to be more specific. What I have now is recurrent BCC. It’s a strange cancer that’s very slow moving. In my case, they don’t believe it has metastasized yet, so I’m not sure if there’s a stage that they could put on that. They just know that it’s marching forward toward my brain at this point. It’s gone from my sinus cavity up through my sinus into the ethmoid (cavity) and is perforating bone there as we speak. So the outlook right now is not very good. My prognosis based on my most recent discussion with my oncologist is the “we’re so sorry” speech because they can’t do much more at this point.

I had gone back onto Erivedge (vismodegib), which is a hedgehog inhibitor, for 51 days. I started in October, and I continued until New Year’s Eve. The toxicity just built up immediately again. Before that, ... I took 227 consecutive doses of Erivedge, then I had taken the whole summer off from Erivedge. I melted down on June 11 last summer from toxicity. And that’s when I stopped taking it for the summer. I went from 128 pounds back up to 165 pounds, which was lovely. I had a great summer, best summer ever. All the side effects went away and my appetite came back. And I’ve actually got little tufts of hair growing here and there now, which had all been gone because (that’s) one of the side effects. My MRIs at the time looked clean, but what they found in the last one in September was they had been looking in the wrong place. If they went back six months and looked where the cancer is now, they could actually see a little spot there. They said, “Oops, sorry.” So I thought I was good for months and months, and evidently, I was not. So that was a little — I don’t know the accurate word to describe that — but it was a little disappointing, let’s just say frustrating.

I met with my doctors at Dana-Farber on January 5, 2021, when I had an MRI and blood work. The results are still not good. If anything, (it) looks a little bigger. My doctor basically talked to me about the odds and the ramifications of trying this immunotherapy, which I wasn’t particularly interested in doing, having read all the side effects, which remind me very much of what I’m experiencing still from the hedgehog therapy. If you don’t do anything, nothing’s going to happen and nothing is going to change, and that’s the path (I’m) heading down. ... My wife and I talked about it. ... We quickly came to an agreement that nothing ventured, nothing gained, so let’s go with the immunotherapy.

Q: What other therapies, if any, did you undergo, and how was it decided for you to be on hedgehog therapy?

A: Because of the location of the recurrent BCC that I have now, previous to (hedgehog therapy), I’d had blue light therapy, which is topical. I’ve had radiation. I had different variations of blue light (therapy) where you sit out in the sun for three hours after they administer this chemo to your head and it basically burns all your head off.

In terms of medicine, the hedgehog (therapy) is the first medication that (I’ve) taken (because) it was determined that we can’t treat this any other way. The options right now for me surgically are none, basically. They can remove my right eye, my right orbital bone, my right cheekbone, my right cheek, my nose and my forehead with a significant amount of bone, which will leave me horribly disfigured. Then they can’t promise that they will have gotten the cancer. So to me, that’s really not an option from a surgical standpoint.

My wife and I have spoken about this at great lengths. (For) the surgery that I had for my nose, they took a vein and a piece of bone from my arm and skin, and they removed my whole nose and built a new nose out of this piece of bone, which is screwed into my skull. And they overlaid that with the skin and the vein. They used a vein and snaked it from the graft that they took and brought it down through my face and down into my neck to feed that. It was a pretty significant surgery. It was 19 hours of operation, and I was at Dana-Farber for eight days or (so). And it took me about a year to recover from that with physical therapy and (from) just emotional shock because it’s pretty invasive and daunting. So I had a couple good years with the new nose. Then we went back and they said, “The cancer’s back in your sinus.” So (it was in) the area that they’d spent all their time reconstructing (so) somehow, there’s something somewhere. (BCC) is very invasive. They describe it to me as sort of a spiderweb of tiny cells that are all dancing to their own beat. They all march wherever they feel like going, and mine seems to be marching north right now toward my brain. So that’s the hand that I’ve been dealt.

Q: How did your cancer team work with you throughout this entire process and how supportive were they?

A: Well, it runs beyond that. I have a dermatologist and a surgeon up (in Maine). I still go to the dermatologist every couple of months because I still have things on my head. I’ve had all three skin cancers. I’ve had squamous (cell carcinoma) and melanoma numerous times. I’m still getting residual squamous (cell carcinoma) in my head. Fortunately, I haven’t had any melanomas in a couple years. I see my dermatologist here, she gets the (pathology) results, she sends me to ... my plastic and hand surgeon, and he does my little surgeries. I call them little ones, but anytime you can be awake and laugh with everybody, that’s a good surgery, not a rough one. So I have those people up here. It’s sort of my core team.

My (primary care provider) through this whole event ... has been critical. There are many spokes on this wheel, and she’s been the hub because insurance companies want your doctor to send them this or that. I’ve literally had probably 10 or 12 doctors in the past 10 years, and it’s very difficult to coordinate 10 different doctors independently. So she’s been the coach for me, my cheerleader and the hub of this wheel to gather all the information and send it to people as needed. So that is part of my health team up here.

The Dana-Farber team is fabulous because of the patient portal and being able to send messages or pictures. After my surgery, a piece of bone fell out of my nose. It looked like a little piece of fish bone. If you’re having a lovely meal out, you’re having fish and you pull this bone out of the salmon, it’s that big. I’m a writer, so I’m writing and this thing goes “clink” on the table. I held it up, I took a picture of it and sent it. (My doctor) laughed and said, “Don’t worry about the detritus of the surgery. That’s fine.” Just getting instant feedback like that, and I could email him and he’d email me back in less than an hour because I have his personal email. I have (the Dana- Farber team’s personal cell phone (numbers). I can text these doctors, and I get a call back in 15 minutes if I need it.

Q: What advice would you give patients in a similar situation to you — when hedgehog therapy isn’t quite working for them to treat BCC?

A: I would do what I did, which is go until you don’t think you can go anymore because I think it ultimately did help me extend my time here to a significant degree. If I had thrown in the towel a few years ago, I probably wouldn’t be here right now. So I guess that and really discussing things. ... I told my oncologist, my dermatologist and my radiologist that I’m not really concerned about quantity at this point, but quality. If I’ve got two years, how can we make this the best two years? My goal at this point is not to wrap this up with a big bow and call it all good because I know that’s not true. Let’s be realistic about this and pragmatic.

I guess the advice that I give everybody as a patient (is that) the hardest part for a patient is just showing up. Everybody else has the tough job. What do we do for this guy? What can I do in surgery for him? As a patient, I just have to put one step in front of the other and move forward. People are always cheering me on and (telling me), “You’re so brave.”

It’s certainly not that at all. Just keep going.

For more information, visit www.skincancerinfo.org. This interview has been edited for clarity and conciseness.

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