A New Dawn for Melanoma Treatment
The Promise of Neoadjuvant Therapy
Melanoma has been a formidable adversary for medical researchers and clinicians. However, a groundbreaking approach known as neoadjuvant therapy is offering hope for a more promising future. This innovative treatment regimen involves administering therapy before surgery, aiming to shrink the tumor and enhance the immune system’s ability to fight cancer cells.
Dr. Sapna Patel, a renowned expert in melanoma and neoadjuvant therapy and Endowed Chair in Cancer Research, Professor of Medicine and Ophthamology and Director of the Cutaneous Oncology Program at the University of Colorado, sheds light on this approach. “Neoadjuvant therapy is like a preemptive strike against the cancer,” she explains. “By treating the tumor before surgery, we can assess its response to therapy and potentially tailor the treatment plan accordingly.”
One of the most significant advantages of neoadjuvant therapy is its ability to provide valuable information about the tumor’s behavior. “By observing how the tumor responds to treatment before surgery, we can gain insights into its aggressiveness and potential vulnerabilities,” Patel notes. This knowledge can help clinicians make more informed decisions about the most effective postoperative treatment.
For example, neoadjuvant therapy shows how effective treatment is and how much treatment was needed to shrink the tumor. If treatment wasn’t as effective, then the clinical team can quickly assess and try alternate treatment options.
While neoadjuvant therapy holds great promise, it’s not without its challenges. One potential drawback is the risk of the tumor spreading during the treatment period. However, Patel emphasizes, “In many cases, the potential advantages of neoadjuvant therapy, such as improved outcomes and reduced surgery, far surpass the risks,” she says. The thinking is that using immunotherapy when cancer is still present (in the neoadjuvant setting), can train the immune system to better identify cancer cells. As such, when the tumor is removed, the stimulated and primed immune system can hunt down any microscopic cancer remnants that may still remain and be prepared in the instance that the melanoma returns.
Another area of ongoing research is the optimal timing and duration of neoadjuvant therapy. Clinicians are exploring the most effective treatment regimens and determining how long to administer therapy before surgery. “The goal is to strike the right balance between maximizing the benefits of neoadjuvant therapy and minimizing risks,” Patel explains.
The work that MRA is funding is helping researchers like Patel better answer these questions. It’s also helping Patel and her group to develop biomarkers that determine if patients have developed memory T-cells that can specifically recognize melanoma. Memory T-cells are types of immune cells that remain long after an exposure to cancer antigens and are able to respond quickly when exposed to the same antigen if the cancer comes back, having the potential to kill the new tumor.
The field of neoadjuvant therapy for melanoma is rapidly evolving, with researchers making significant strides in understanding its mechanisms and optimizing its application. It is being compared to approved adjuvant therapy, treatment after surgical removal of cancer. Patel led a recent study, the SWOG S1801 phase II trial demonstrating that neoadjuvant immunotherapy followed with adjuvant immunotherapy after surgery had a superior event-free survival compared to just treating with adjuvant immunotherapy alone post-operatively. Another large, randomized study known as NADINA phase III trial using neoadjuvant combination immunotherapy followed by surgery and adjuvant therapy administered based on the response to neoadjuvant treatment, resulted in longer event-free survival than surgery followed only by adjuvant immunotherapy. Both studies were shared at large international forums and have garnered significant attention, further highlighting the important role that melanoma research is playing in the cancer field and advancing neoadjuvant therapy potentially as the new standard of care.
“As these two studies mature over the next few years, we will hopefully shed some light on the role of what you need to do at the surgical level and post-operatively if you’ve received neoadjuvant immunotherapy,” says Patel. “For example, “Can we minimize the surgery? If you’re having such a strong response to neoadjuvant therapy, do you need the big surgery or can you have a more minimal surgery? Can you omit the surgery? Maybe people can have complete eradication of their tumor with neoadjuvant therapy alone. And if you’re really able to drop adjuvant therapy or minimize it, will there be shorter durations of treatment overall?”
As Patel notes, “The future of melanoma treatment is promising, and neoadjuvant therapy is playing a pivotal role in shaping that future.” By providing valuable insights into tumor behavior and offering the potential for improved outcomes, this innovative approach is paving the way for a more effective and personalized treatment paradigm. As researchers continue to explore the possibilities of neoadjuvant therapy, patients with melanoma have more options available to them than ever before. 
Dr. Sapna Patel
