Expert: Immunotherapies, Targeted Therapies Show Promise in Melanoma

In an interview with Pharmacy Times at the Oncology Pharmacists Connect conference in Austin, Texas, Heidi Finnes, PharmD, BCOP, FHOPA, director of clinical ambulatory pharmacy practice at Mayo Clinic, discussed updates in melanoma and the use of immunotherapies and targeted therapies. With a growing armamentarium of options for these patients, Finnes also discussed sequencing and optimal combination therapies for different patients.

Q: Can you give a brief overview of melanoma as a disease state?

Heidi Finnes, PharmD, BCOP, FHOPA: Sure. So, melanoma is a disease of the skin most often. Patients who have blond hair, blue eyes, you know, light skin tones, who sunburn easily can be at higher risk. But melanoma can also not be related to the sun whatsoever. Sometimes you can get it between the webs of your toes, underneath your nails, things like that as well. It's a disease that's treated primarily now by immunotherapy, so it doesn't respond well to traditional chemotherapy-type agents that we think of when people say that they have cancer. About 50% of people can have a mutation called BRAF, and having that mutation makes you eligible for certain types of targeted therapies. So again, with melanoma, you can have melanoma, and actually no one might know it because you don't lose your hair or have the side effects that you think of because you don't give traditional treatments like chemotherapy.

Q: Which patients are most likely to see success with immunotherapy?

Heidi Finnes, PharmD, BCOP, FHOPA: So, I think any patient really receives immunotherapy as a first line treatment for cutaneous melanoma. Most treatments are programmed death-1 (PD-1) inhibitors, things like you see on TV—nivolumab or Opdivo, Keytruda or pembrolizumab. Other agents that you can receive if you have that BRAF mutation, like I talked about, targeted therapies, and there's a multitude of those combinations of treatments that patients can receive.

Q: What are the available immunotherapies approved for melanoma.

Heidi Finnes, PharmD, BCOP, FHOPA: So, the available immunotherapies approved as single agents are things like pembrolizumab. Those –mabs tell you that it's a monoclonal antibody at the end of the word. Pembrolizumab or Keytruda, Opdivo or nivolumab. In combination, sometimes we see drugs like atezolizumab or Tecentriq, and those agents can be used in combination with other things like ipilimumab or Yervoy.

Q: How are immunotherapies typically sequenced and best used in the broader treatment plan for melanoma?

Heidi Finnes, PharmD, BCOP, FHOPA: So, I think the sequence really depends on how the patient presents and the disease that the patient has. In patients who are highly symptomatic, usually we treat those patients with medications that are going to act more quickly. If they have that BRAF mutation, oftentimes, we will give the BRAF [or] MEK inhibitors as first line therapy to try to gain control of the disease. And then subsequently we will start the immunotherapy types of agents after that. If patients are not symptomatic, then it's really kind of a toss-up. You can start with dual checkpoint inhibitors. Information that was presented at ASCO with the RELATIVITY-47 trial talked about a first line dual checkpoint nivolumab plus a LAG-3 inhibitor, relatlimab. Or we also know that patients can get ipilimumab or Yerboy and nivolumab in combination first line as well.

Q: Turning to targeted therapies, what gene mutations are typically seen in melanoma that could be targeted with these therapies?

Heidi Finnes, PharmD, BCOP, FHOPA: So, as I mentioned, the BRAF mutation is the most common. V600e or V600K, that's in about 50% of melanoma patients, and that opens up then treatment for patients with that mutation with BRAF [or] MEK inhibitors. We can also see mutations like C-kit, where we might use agents like imatinib or defactinib, some of those types of agents, if patients harbor a C-kit mutation. Also, we can target with different medications that are specifically approved for NRTK mutations, as well.

Q: What considerations should clinicians be aware of when considering inhibitors for these kinds of mutations?

Heidi Finnes, PharmD, BCOP, FHOPA: Okay. So, I think the biggest thing is comorbidities and concurrent medications that patients may be taking, because that would lead me to potentially select, you know, different combinations of those BRAF and MEK inhibitors. You know, the good thing is that patients with cancer are living longer, but unfortunately, that means many of them have comorbidities like diabetes and hypertension and are on lots of different medications that can cause drug-drug interactions. And so, I think those are the things. Getting an accurate medication list, you know, maybe having a pharmacist help, to be sure of the types of side effects that patients may have with current medications that they're on before selecting the appropriate targeted therapy, I think is helpful.

Q: Some melanomas, particularly mucosal melanoma and ocular melanoma, have much more unique challenges. So how are immunotherapies or targeted therapies potentially used here?

Heidi Finnes, PharmD, BCOP, FHOPA: So, we do still use immunotherapies for those types of patients, but often they don't respond as well. Specifically uveal melanoma just had a recent approval of a medication called tebentafusp-tebn, which is bispecific monoclonal antibody or bispecific protein that it binds to, but you have to have a certain type of HLA typing in order to receive that therapy. In the clinical trial, it compared the tebentafusp-tebn to standard of care pembrolizumab, I believe it was dacarbazine chemotherapy. And the benefit, I believe, was quite substantial, favoring tebentafusp-tebn. And so again, it's finding those unique things to those types of melanoma that maybe don't respond as all the cutaneous types of melanoma do.