Summary: The Next Decade of Melanoma Treatment
Last updated: March 2023
Last month, our SkinCancer.net editorial team attended The Melanoma > Exchange Patient & Advocate Forum in Washington D.C. It was a half-day meeting hosted by the Melanoma Research Alliance that brings together patients, their families, industry leaders, and melanoma clinicians and researchers. It was a great forum for these different groups to learn from each other, get and receive support, and discuss hope for the future.
The next decade of melanoma treatment
One of the most interesting presentations throughout the day was: Looking Beyond 2020 - The Next Decade of Melanoma Treatment. It was a presentation and panel discussion with world-renowned researchers: Dr. Marlana Orloff (Thomas Jefferson University), Dr. Georgia Beasley (Duke University), Dr. Kenneth Grossman (University of Utah), Dr. Stephanie Goff (National Cancer Institute), Dr. James Moon (University of Michigan), and Dr. Antoni Ribas (UCLA).
The long road of melanoma research
Dr. Orloff began by explaining that we have come a long way, but we have more work to do in the world of melanoma research and treatment. Every case of melanoma is different and can follow very different courses, especially when it comes to the rare sub-types. They respond differently to the current treatments of targeted therapy and immunotherapy, and even if they do respond, resistances can develop over time. Brain metastasis and liver metastasis are among the most difficult to treat.1
The latest melanoma research and clinical trials
Combination strategies are advancing, specifically, triplet therapies for BRAF mutated melanoma. Why triplet therapy? Many of the current combination therapies are not hitting long term benchmarks, currently reaching 20% - 40% for 4-5 year survival, depending on the specific therapy. So, the industry needs to do better. PD1 and BRAF inhibitors become resistant and researchers have learned a lot about them over time. Triplets that include BRAF inhibitors and immunotherapy, have some early data and it’s looking good, but they need more mature durable data. However, one exciting benchmark is 24-month progression survival. The triplet therapy, compared to the BRAF inhibitor alone, doubles survival rate from 20% to 40%.1
Adjuvant and neoadjuvant therapy
Adjuvant therapy is additional cancer treatment, after the primary treatment, aimed to lower the risk that cancer comes back. It is typically treatment after surgery. It focuses on treating patients at earlier stages and is finally in practice for some patients. They can offer these targeted therapies and can reduce the chance that a patient's cancer comes back by 50%. There are potentially toxicities, so they need to spend time figuring out who really needs it.1
Neoadjuvant therapy is systemic therapy to treat the whole body before surgery. It can reduce the tumor and make surgery easier. It also allows pathologists to determine if the therapy worked once the tumor is removed. If it worked, clinicians keep using the therapy, if not, they try something else. One risk is, what if it spreads before they take it out, while they're trying to treat it? They follow patients closely and if it’s not working, they take them to surgery right away.1
If T-cell lymphocytes infiltrate a tumor it is a tumor-infiltrating t-cell (TIL). If they excite all T-cells in the body to fight the melanoma and it’s only working for 4% of patients, how can they be more targeted? They started to see a big impact with tumor-fighting lymphocytes. They've used TIL with 220 patients with metastatic melanoma and have a complete response rate of about 25%. Better than 4%, but not perfect! It is a learning tool as well that they're using in other cancers. Many people think if a patient doesn't respond to checkpoint therapy, TIL won't work, but that's not true. There's something about what they do with TIL that’s different than other drugs. It is not an easy treatment to go through or prepare, so it's important to find the right patients to treat.1
One lab that develops new drug therapeutics, is focused on synergizing immune checkpoint blockers, so it can work for more patients. One of the main challenges is patients who respond have a lot of anti-tumor lymphocytes already (about 25%). What about patients who aren't responding to the immune checkpoint blockers? One answer is a cancer vaccine. They hope to train enough number of t-cells to fight against tumor cells - they’ll infiltrate into the tumor. There have been good results with mice studies so far and they are pushing toward clinical trials. Another thing to consider is how to recruit t-cells to tumor tissues. One approach is the impact gut microbiome can have. Patients that respond well to immune checkpoints have a diverse microbiome, we’re trying to understand the relationship with t-cell immunity and immune checkpoints. It's a work in progress.1
Intralesional therapies involve injecting a therapy in one part of the body and have it work in another part of the body. One system we have that works all over the body is the immune system. Can they train it to attack the melanoma? It typically finds something that’s wrong and attacks it, in other locations in the body, and even years later (same way vaccinations work). Can they use the melanoma to turn it into a vaccine? They're working to inject something into melanoma so that the immune system thinks something is really wrong. Usually, they see that the immune system isn’t doing anything to the melanoma. It’s like lighting the first match and having the fire spread. It will work best if they boost with immune checkpoint therapy.1
If you’re interested, the full panel discussion can be viewed here.
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