https://www.cancer.gov/news-events/cancer-currents-blog/2022/melanoma-immunotherapy-before-surgeryThe treatment landscape for melanoma has witnessed remarkable transformations in the past decade, making it one of the most rapidly evolving fields in cancer care. Promising results from an NCI-funded clinical trial indicate that another breakthrough in the treatment of this aggressive form of skin cancer is on the horizon. The trial focuses on enhancing treatment outcomes for individuals with advanced melanoma who are still eligible for surgery.

The trial divided participants into two groups: one group underwent surgery to remove tumors and received periodic doses of the immunotherapy drug pembrolizumab (Keytruda) as adjuvant therapy over the following year, while the other group received several doses of pembrolizumab before surgery (neoadjuvant therapy), followed by adjuvant therapy with pembrolizumab for 10 months after surgery.

The results showed that the group receiving neoadjuvant treatment had a significantly lower risk of cancer recurrence compared to those who received only adjuvant treatment. Notably, approximately 20% of patients treated with pembrolizumab before surgery experienced complete disappearance of their original tumors. These findings were presented at the European Society for Medical Oncology (ESMO) meeting in Paris.

While the trial, led by Dr. Sapna Patel from the University of Texas MD Anderson Cancer Center, has not yet determined if neoadjuvant therapy with pembrolizumab improves overall survival, the results thus far are highly encouraging. Dr. Patel believes that professional oncology organizations may revise treatment guidelines to recommend the consideration of neoadjuvant pembrolizumab for individuals with melanoma.

Impact of Neoadjuvant Therapy and Immune Response: Adjuvant therapy has become a standard practice for treating many cancers, including melanoma. Its purpose is to eliminate any residual cancer cells that were not removed during surgery and to target any undetectable micro-metastases within the body. In the trial, referred to as S1801, participants had melanoma that had spread to nearby tissues or even distant parts of the body, but surgery was still deemed effective for their treatment.

By starting immunotherapy before surgery, the trial aimed to leverage the immune response already present in and around the tumors. These immune cells are already aware of the tumor’s existence but may not be strong enough to destroy it. The neoadjuvant approach aimed to boost this immune response and facilitate a more effective attack on the tumor.

Improving Event-Free Survival: The phase 2 trial enrolled 313 patients with stage 3 or 4 melanoma. Participants were randomly assigned to either receive surgery followed by 18 doses of pembrolizumab over a year as adjuvant therapy or receive the first three doses of pembrolizumab before surgery and the remaining 15 doses over the 10 months following surgery.

The primary measure of the study was event-free survival, which refers to the duration individuals live without experiencing specific events related to cancer. After 2 years, 72% of the neoadjuvant therapy group remained alive without events, compared to 49% in the adjuvant therapy group. Notably, the neoadjuvant therapy group had significantly fewer cases of cancer recurrence during the adjuvant therapy period.

Implications and Future Research: The trial’s findings have implications for the treatment of stage 3 or 4 melanoma. While the approach to melanoma treatment can vary across different hospitals, experts, including Dr. Teresa Petrella from the Sunnybrook Odette Cancer Centre in Toronto, agreed that neoadjuvant and adjuvant therapy appears to be more effective than adjuvant therapy alone.

Further research is needed to explore potential combinations of neoadjuvant immunotherapy drugs and to determine if patients with complete eradication of tumors after neoadjuvant therapy require less adjuvant therapy. However, the findings suggest a paradigm shift in melanoma treatment, with leaving the cancer in place for a short period before surgery potentially proving preferable to immediate surgical intervention.

The use of neoadjuvant immunotherapy, particularly pembrolizumab, shows promise in enhancing treatment outcomes for individuals with advanced melanoma who are still eligible for surgery. The trial’s results indicate a lower risk of cancer recurrence and the potential for complete tumor disappearance after neoadjuvant therapy. This may lead to revised treatment guidelines and a shift in the treatment paradigm for melanoma and potentially other cancers. While further research is needed, neoadjuvant therapy represents a significant advancement in improving patient outcomes and changing the timing and approach to melanoma treatment.

Source :https://www.cancer.gov/news-events/cancer-currents-blog/2022/melanoma-immunotherapy-before-surgery