Sapna P. Patel, MD, on Melanoma: New Data on Pembrolizumab, Adjuvant vs Neoadjuvant Plus Adjuvant

The rationale behind neoadjuvant immunotherapy for melanoma is that cancer comes in contact with T cells that are inside the tumor. If you remove the tumor, you remove those T cells with it. On the other hand, if you give neoadjuvant therapy while the tumor is still in place and those T cells, you end up generating a larger immune response than if you give the same treatment after the tumor is removed. With that in mind, we designed the SWOG S1801 phase II trial. The study was a randomized one-to-one study for participants with stage IIIB to IV resectable melanoma. Participants on the adjuvant arm were randomized to surgery first followed by 18 doses of adjuvant pembrolizumab, flat-dosed every three weeks. Participants on the neoadjuvant arm received 3 doses of pembrolizumab followed by surgery, and then 15 doses of adjuvant pembrolizumab. Neoadjuvant therapy with pembrolizumab followed by adjuvant pembrolizumab improves event-free survival in resectable melanoma. Toxicities were well-managed and no new safety signals emerged. In fact, the use of neoadjuvant pembrolizumab did not lead to an increase in surgery events. Compared to the same therapy given entirely after surgery, the use of neoadjuvant pembrolizumab improves event-free survival in patients with resectable melanoma. The next steps for S1801 include central pathologic review on the neoadjuvant specimens to determine a correlation between pathologic response and clinical outcomes. Future neoadjuvant studies can consider S1801 as a benchmark and expand on deescalation of surgery protocols, deescalation of adjuvant therapy, or escalation of neoadjuvant or adjuvant regimens for those whose tumors do not respond.