Combination Therapy Before Surgery Shows Promise for Aggressive Skin Cancer
Researchers at Moffitt Cancer Center are exploring a new treatment strategy that could improve outcomes for patients with Merkel cell carcinoma, a rare but aggressive form of skin cancer. In a phase 2 clinical trial led by Andrew Brohl, MD, a medical oncologist at Moffitt, the combination of lenvatinib and pembrolizumab given before surgery showed encouraging results, with more than half of patients achieving a complete response. The findings were presented at the 2025 Society for Immunotherapy of Cancer Annual Meeting.
Today at #SITC25: Don't miss Daniel Abate-Daga, PhD and Kenneth Tsai, MD, PhD (@KYTsaiLab) share groundbreaking cellular therapy research. #MoffittSITC25 pic.twitter.com/kaDqHniCw4
— Moffitt Cancer Center (@MoffittNews) November 7, 2025
Merkel cell carcinoma is considered one of the most challenging skin cancers to treat because of its high risk of recurrence and spread.
“Merkel cell carcinoma has a high propensity for metastatic dissemination and is associated with about a 40% recurrence rate,” said Kenneth Tsai, MD, PhD, co-leader of the study and co-director of the Donald A. Adam Melanoma and Skin Cancer Center of Excellence at Moffitt. “It’s also often missed clinically because of its somewhat nonspecific appearance on the skin.”
Testing Immunotherapy Before Surgery
Kenneth Tsai, MD, PhD
The study tested immunotherapy in the neoadjuvant setting, meaning treatment was given before surgical removal of the tumor.
“This method of treatment is modeled on the tremendous success seen in melanoma,” Tsai explained. “The goal is to excite an immune response while there is still some tumor present, reducing tumor burden and helping the body recognize cancer cells in the future.”
The treatment paired lenvatinib, a drug that blocks multiple signaling pathways involved in tumor growth and blood vessel formation, with pembrolizumab, a checkpoint inhibitor that helps the immune system recognize and attack cancer cells.
“Lenvatinib targets pathways that can make tumors more immunosuppressive,” Tsai said. “By combining these two drugs, we may make immunotherapy more effective.”
This combination has already shown success in several other cancers, including endometrial cancer.
Encouraging Early Results
More than half of patients in the trial had a complete pathological response, meaning no detectable cancer remained at the time of surgery.
“The great news is that we have effective treatment options for a substantial proportion of patients with Merkel cell carcinoma,” Tsai said. “But we can always do better.”
Currently, there is no FDA-approved standard for neoadjuvant therapy in Merkel cell carcinoma. However, studies like this one are building strong evidence that treating patients before surgery could improve outcomes and reduce the risk of recurrence.
“We know from real-world experience and from previous trials that neoadjuvant therapy is highly effective in Merkel cell carcinoma,” Tsai said.
Learning From the Tumor’s Response
Beyond its immediate impact on patients, Tsai said this research also provides valuable insight into how the immune system interacts with tumors during treatment.
“Neoadjuvant therapy is particularly compelling because there’s an opportunity not only to lessen the morbidity of surgery but to combine the best of both worlds using the immune system and then physically removing what’s left,” Tsai explained. “Because the tumor beds are removed, we can study how the tumor microenvironment evolves over the course of therapy and gain insight into what immune features are needed to develop curative treatments.”
Researchers hope this combination approach will continue to show promise as a way to improve survival for patients with Merkel cell carcinoma and potentially pave the way for more personalized immunotherapy strategies in the future.
