UH Seidman Oncologists Help Chart New Path for Advanced Melanoma Patients
May 09, 2023
Innovations in Cancer | Summer 2023
Patients undergoing surgery for Stage III or Stage IV melanoma have significantly better outcomes if they receive the immunotherapy checkpoint inhibitor pembrolizumab (Keytruda) both before and after surgery, according to the results of a Phase 2 clinical trial recently published in The New England Journal of Medicine and co-authored by UH Seidman Cancer Center oncologists Ankit Mangla, MD, and Amy M. Reese, MD. These findings have the potential to change the standard of care for these patients, they say, and add to the growing body of knowledge supporting the use of neoadjuvant therapy in oncology.
Dr. Mangla, Dr. Reese and a team of national oncology colleagues randomly assigned 313 patients with clinically detectable, measurable Stage IIIB to IVC melanoma to three doses of neoadjuvant pembrolizumab, then surgery, then 15 doses of adjuvant pembrolizumab (neoadjuvant–adjuvant group) or to surgery followed by pembrolizumab (200 mg intravenously every three weeks for a total of 18 doses). Treatment continued for approximately one year or until disease recurred or unacceptable toxic effects developed (adjuvant-only group). The primary end point of the study was event-free survival.
Results show that event-free survival at two years was 72 percent in the neoadjuvant–adjuvant group, compared with just 49 percent in the adjuvant-only group. Importantly, the percentage of patients with treatment-related adverse events of grades 3 or higher during therapy was 12 percent in the neoadjuvant–adjuvant group and 14 percent in the adjuvant-only group.
“Among patients with resectable Stage III or IV melanoma, event-free survival was significantly longer among those who received pembrolizumab both before and after surgery than among those who received adjuvant pembrolizumab alone,” Dr. Mangla says. “No new toxic effects were identified.”
The melanoma team at UH Seidman expects these findings to have a major impact going forward.
“The results of this study represent the largest Phase 2 clinical trial experience with neoadjuvant therapies in melanoma,” says Luke D. Rothermel MD, MPH, Chief, Section of Soft Tissue and GI Surgery in the Division of Surgical Oncology at UH Seidman Cancer Center. “This is a major effort that will likely change the paradigm of treatment for people with melanoma. Our patients who participated in this trial have made a real impact on the future of this disease. I am proud of our multidisciplinary team that drove this effort forward.”