Addressing Skin Cancer: From Screening to Treatment

Meredith McKean, MD, MPH

In the United States (US), The U.S. Preventive Services Task Force (USPSTF) continues to push forth recommendations to stop diseases like skin cancer from developing. However, skin cancer still impacts approximately 9,500 Americans each year, according to the American Academy of Dermatology.

According to Meredith McKean, MD, MPH, the USPSTF does not recommend screening everyone. Considering that skin cancer is imminent for some individuals, much work has been done to improve the treatment landscape for patients with skin cancer. In the upfront setting, the disease can potentially be eliminated, explained McKean, director of Melanoma & Skin Cancer Research, Sarah Cannon Research Institute and medical oncologist at Tennessee Oncology, in an interview with Targeted Oncology™.

“As the USPSTF states, there is insufficient non-randomized randomized data, which is the strongest data to advise and be able to link an early diagnosis with better treatments. We know that trying to catch skin cancer early on improves outcomes for patients, because if you can diagnose an early squamous cell carcinoma, basal cell carcinoma, or melanoma, these patients can be cured with surgery alone. That’s really the goal, to try to diagnose these as early as possible, because that opens up more treatment options,” said McKean.

For patients with advanced skin cancer, McKean explained that new immunotherapy and targeted therapy options have either entered the market or are available to patients through enrollment in ongoing clinical trials.

In the interview, McKean reviewed the recent changes to the screening guidelines, and advances in the skin cancer treatment paradigm.

What should oncologists know about the recent update to the USPSTF guidelines?

McKean: The USPSTF guidelines are looking across a population of the US and trying to issue guidelines for the general population as far as cancer screening goes. The latest update is that they said there remains insufficient evidence to broadly recommend every person to have an annual skin check performed. Now, this does not pertain to patients on an individual level. It pertains to patients that may be at higher risk for developing skin cancer, have a strong family history of skin cancer, or have a personal history of skin cancer. It's important to take that into consideration for the individual patient in front of you. The guidelines do not recommend blanket screening for all patients for skin cancer.

Can you discuss some of the therapeutic options for patients who are diagnosed with skin cancer?

As the USPSTF states, there are insufficient non-randomized randomized data, which are the strongest data to advise and be able to link an early diagnosis with better treatments. We know that trying to catch a skin cancer early on improves outcomes for patients, because if you can diagnose an early squamous cell carcinoma, basal cell carcinoma, or melanoma, these patients can be cured with surgery alone. That’s really the goal, to try to diagnose these as early as possible, because that opens more treatment options for local therapies that really tried to take care of the cancer before there is a higher risk of it spreading elsewhere.

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The primary treatments for patients that are eligible would be surgically removing the tumor that would be applicable for any of the common skin cancers, or patients that aren't able to undergo surgery. If the tumor is in a more challenging location, there are other options that patients can consider with dermatologists including different topical therapies, cryotherapy, and other options including radiation, and systemic therapies. That's usually not an option until these tumors are too large for local therapies such as surgery, radiation, or topical therapies.

What outcomes can oncologists expect with the available therapies?

We're getting better at understanding tumors on a molecular level. Historically, especially for melanoma, we've always looked at the depth of a tumor to say, how aggressive is this tumor? What's the likelihood of it to come back? But we are learning more on a molecular level, what a more aggressive tumor looks like vs a less aggressive tumor. That's helping us identify the patients that are at higher risk for this cancer to return. In general, it doesn't change our management up front. But we are learning more, and I think that's where we may see the introduction of earlier systemic therapy.

We now have an FDA approval for patients with stage IIB or IIC melanoma. Even though these patients have undergone that standard surgical treatment, and we have not found any cancer in the lymph nodes, these patients still benefit from adjuvant immunotherapy or a year of immunotherapy to try to address the cancer on a systemic level throughout the body. I think the expectation is that undergoing surgery and really trying to remove all the tumor upfront for these early melanomas, the expectation should still be there. But it is worthwhile to look our patients who have higher risk tumors and see if there are any other options that we should be looking at to try to prevent this cancer from coming back.

Can you expand on the therapies available for late-stage skin cancer?

The drug relatlimab with nivolumab [Opdualag] is another FDA-approved option for patients with metastatic melanoma. We're seeing a lot of development looking at cellular therapies. [For] 1 therapy, tumor infiltrating lymphocytes [TILs], we're seeing additional data that looks like that's going to be a beneficial treatment for patients. That treatment involves patients undergoing surgery to remove 1 of the tumors in their body, the lymphocytes in the tumor that we think clearly got attracted to that tumor but are just not as active as we'd like them to be not as high number. These TILs are removed, they're stimulated in vivo, and then reinfused into the patient. This patient receives chemotherapy beforehand, and then high dose interleukin-2 afterwards. It's a therapy that's been in development for a number of years. But we're excited to see further development there, in addition to other immune therapies that are ongoing in clinical development.

Additionally, in the metastatic setting, in a we have had FDA approved treatments for BRAF V600 mutations. But we're now seeing development of other pan RAF inhibitors that would apply to patients with other BRAF mutations that we know are very common in melanoma. We know NRAS mutations are present in about 10% to 20% of patients, we now have clinical trial options for those patients. I think it's been exciting to see more targeted therapy options evolve for all those patients that we haven't had treatments for that are BRAF wild type in the stage III settings. These are patients that have undergone surgery, and we're looking at systemic therapy for these patients.

There's also been a lot of excitement with neoadjuvant therapy. We now know, based on the SWOG S1801 data [NCT03698019] that even for standard of care, immune checkpoint inhibitors, such as pembrolizumab [Keytruda], offering that in starting with 3 doses before surgery is more beneficial than starting after surgery. That's been exciting to see, and it has been a change in our practice, to start that treatment before surgery.

We're seeing a lot of exciting adjuvant therapy in patients after their tumor has been removed. One of the exciting trials was the personalized cancer vaccine that had recently published data showing an mRNA-4157 personalized cancer vaccine combined with pembrolizumab versus pembrolizumab alone, significantly improved relapse-free survival [NCT03897881]. I think that's exciting technology, and there's a lot of interest in seeing that next development in a phase 3 study.

Given the many recent advances in the space, what is your key advice for oncologists who treat skin cancers?

Over the past year, melanoma has been very quickly evolving. We now have new options, like I said, for patients with stage II through stage IV melanoma. We also have new treatments in the neoadjuvant setting, in addition to a lot of exciting trials in the adjuvant setting.

I think the key advice is certainly looking at each patient to see which the clinical trial options are for these patients, and then making sure that they’re doing that molecular profiling, especially in the metastatic setting, to understand what's driving that individual patient's cancer.If there’s a BRAF V600 mutation, we have targeted therapies for that. But again, if it's another atypical BRAF mutation and RAS mutation, or CDKN2A loss, we have several trials available for those patients. That's been an exciting advance.