Tumors from desmoplastic melanoma, a rare cancer most commonly found on the head or neck, can often be shrunk significantly before surgery by an immunotherapy known as PD-1 blockade, a result that may reduce the need for disfiguring surgery and radiation. These are the findings of a small clinical trial in this disease by researchers from SWOG Cancer Research Network, a cancer clinical trials group funded by the National Cancer Institute (NCI).

The trial, known as S1512, was led by Kari Kendra, MD, PhD, a SWOG investigator and medical oncologist with The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James). Dr. Kendra will present these results at the American Society of Clinical Oncology (ASCO) 2022 annual meeting in Chicago on June 5 (abstract 9502). 

Although the trial did not directly test whether successful immunotherapy resulted in less extensive surgery and radiation, researchers anticipate such an outcome.

“While this study looked at the impact of neoadjuvant therapy and not surgical intervention, given the significant responses we saw to neoadjuvant immunotherapy in some patients, this study suggests that up-front treatment may spare some from disfiguring surgeries,” said Dr. Kendra, who also serves as professor of internal medicine and chair of the Melanoma Disease Specific Research Committee at The Ohio State University Wexner Medical Center.

Desmoplastic melanoma is a rare form of malignant skin cancer that occurs on sun-exposed areas of the body. It’s a cancer in which local relapse is common, so the standard of care is surgery with wide excision margins followed by radiation therapy. These wide margins and the fact that the cancer is most commonly found on the head and neck mean treatment often leaves patients with large, disfiguring scars. 

Earlier research found that desmoplastic melanoma that had spread, or metastasized, often responded to a type of immunotherapy known as PD-1 blockade therapy. Dr. Kendra’s team hypothesized that treatment with this type of immunotherapy before surgery could shrink these tumors, potentially allowing for less extensive surgery and radiation. 

To test this hypothesis, trial researchers enrolled patients with desmoplastic melanoma that was considered to be operable. A total of 29 patients were treated with 200 mg of the PD-1 inhibitor pembrolizumab every three weeks. Patients received an average of three cycles of this treatment before undergoing surgery to remove their tumors.

More than one-half of the patients who were eligible to proceed with surgery (16 of 29, or 55 percent) showed a pathologic complete response to the immunotherapy, meaning that tissue samples removed during surgery showed no signs of cancer. Patients tolerated the immunotherapy well, with therapy-related adverse events (side effects) being infrequent and of a low grade. Response rates (including complete response, partial response, and stable disease) at nine weeks of treatment were 92 percent, suggesting a high potential for further benefit.
 

Study S1512 is supported by the National Cancer Institute (NCI), part of the National Institutes of Health (NIH), led by SWOG, and conducted by the NIH-funded National Clinical Trials Network (NCTN). The study was funded by the NIH/NCI through grants CA180888 and CA180819 and in part by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. 

In addition to Kendra, the S1512 study team included James Moon, MS, of SWOG Statistics and Data Management Center; Zeynep Eroglu, MD, of Moffitt Cancer Center; Siwen Hu-Lieskovan, MD, PhD, of Huntsman Cancer Institute at the University of Utah; Katie M. Campbell, PhD, UCLA, Jonsson Comprehensive Cancer Center; William Carson III, MD, of the Ohio State University Comprehensive Cancer Center; David Wada, MD, of Huntsman Cancer Institute at the University of Utah; Jose A. Plaza, MD, of the Ohio State University Comprehensive Cancer Center; Gino In, MD, of University of Southern California School of Medicine; Alexandra Ikeguchi, MD, of University of Oklahoma Health Sciences Center; John Hyngstrom, MD, of Huntsman Cancer Institute at the University of Utah; Andrew Brohl, MD, of Moffitt Cancer Center; Bartosz Chmielowski, MD, PhD, of University of California Los Angeles; Nikhil Khushalani, MD, of Moffitt Cancer Center; Joseph Markowitz, PhD, of Moffitt Cancer Center; Marcus Monroe, MD, of Huntsman Cancer Institute at the University of Utah; Kenneth F. Grossmann, MD, of Huntsman Cancer Institute at the University of Utah; Vernon Sondak, MD, of Moffitt Cancer Center; Elad Sharon, MD, MPH, of the NCI’s Cancer Therapy Evaluation Program; Shay Bellasea, MS, of SWOG Statistics and Data Management Center; Michael Wu, PhD, of SWOG Statistics and Data Management Center; and Antoni Ribas, MD, PhD, of University of California at Los Angeles.

Reference: Kendra KL et al, “Neoadjuvant PD-1 blockade in patients with resectable desmoplastic melanoma (SWOG 1512),” J Clin Oncol 40, 2022 (suppl 15; abstr 9502) 

 

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