Neoadjuvant pembrolizumab may significantly improve the management of desmoplastic melanoma, increasing the likelihood of successful resection and reducing the need for further surgery or radiation therapy, according to the response data presented at the 2022 ASCO Annual Meeting, with the surgical considerations presented at the 2023 Society of Surgical Oncology (SSO) International Conference on Surgical Cancer Care.1
Vernon K. Sondak, MD,
Results of the SWOG S1512 study demonstrated high rates of pathologic response and low rates of positive margins in patients with stage II to III desmoplastic melanoma who received neoadjuvant pembrolizumab. Study co-investigator, Vernon K. Sondak, MD, Chair of the Department of Cutaneous Oncology at the H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, called the results “astonishing” for this challenging patient population, suggesting that further evaluation of this treatment strategy is warranted.
“Surgery was safely carried out after neoadjuvant anti–PD-1 immunotherapy, allowing for resection in virtually all patients,” said Dr. Sondak. “Moreover, pathologic response rates were very high compared with expectations from clinical trials in nondesmoplastic melanoma, where one to three doses of single-agent pembrolizumab was associated with a pathologic complete response rate of 20% to 30%.”
As Dr. Sondak explained, desmoplastic melanoma is a rare but important subtype of melanoma, often presenting with deeply invasive, locally advanced disease. Wide excision of the tumor frequently creates large defects requiring complex reconstruction, with a high risk of local and distant relapses.
“Desmoplastic melanoma is associated with a very extensive sun and ultraviolet exposure history, leading to a high tumor mutation burden due to the associated ultraviolet damage,” said Dr. Sondak. He noted that a retrospective study demonstrated that metastatic disease has been shown to be responsive to single-agent anti–PD-1 immunotherapy.
Given the responsiveness of this type of tumor to immunotherapy, the SWOG Cancer Research Network aimed to evaluate the role of neoadjuvant pembrolizumab in patients with desmoplastic melanoma before surgery. Cohort A of the SWOG S1512 study was a single-arm trial, involving 29 patients with resectable stage IIB, IIC, or III desmoplastic melanoma who had residual tumor and no prior immunotherapy. Patients had a good performance status and received 3 weeks of pembrolizumab before any planned surgery. The goal was to proceed directly to surgery after the third dose of pembrolizumab or, if necessary, to give a fourth dose before surgery. Principal Investigator Kari Kendra, MD, PhD, Associate Professor of Internal Medicine, at Ohio State University, Columbus, originally presented data from the trial at the 2022 ASCO Annual Meeting. Dr. Sondak’s presentation focused on the surgical considerations arising from this trial.
Kari Kendra, MD, PhD
Of the 28 patients who underwent surgery, 26 had wide excision of primary or recurrent disease. “No residual viable tumor was found in an astonishing 81% of these wide excision specimens, including one patient who received only one dose because of colitis,” he commented.
Two patients (8%) required reexcision to obtain negative margins, and one of them received postoperative radiation therapy. “In the absence of neoadjuvant therapy, we would expect most of these patients to be candidates for postoperative radiation,” said Dr. Sondak.
Sentinel lymph node biopsy was performed in 17 patients with clinically node-negative disease, with 1 found to have a positive node. Lymphadenectomy was performed on three additional patients with clinical stage III disease; one (33%) had residual viable tumor. After a median follow-up of 24 months, there have been two local recurrences, both in patients who did not have a pathologic complete response, and one of these patients has died of melanoma.
Finally, Dr. Sondak emphasized that the pathologic response rates observed in this study were much higher than those expected compared with nondesmoplastic melanoma trials. A similar drug regimen of one to three doses of pembrolizumab would be associated with a pathologic response rate of between 20% and 30%, he said, which is “maybe half of what was observed in this study.”2
“[T]hese initial results provide hope for improved outcomes in this challenging patient population,” Dr. Sondak concluded.
DISCLOSURE: Dr. Sondak has served as a consultant to Alkermes, Bristol Myers Squibb, Eisai, Genesis Drug Discovery & Development, Iovance, Merck, Novartis, Regeneron, and Ultimovacs and has received research funding from Neogene Therapeutics, Skyline, and Turnstone.
1. Sondak VK, Bellasea SL, Hyngstrom JR, et al: Neoadjuvant pembrolizumab in stage II–III desmoplastic melanoma (SWOG S1512). 2023 International Conference on Surgical Cancer Care. Abstract 57. Presented March 22, 2023.
2. Patel SP, Othus M, Chen Y, et al: Neoadjuvant-adjuvant or adjuvant-only pembrolizumab in advanced melanoma. N Engl J Med 388:813-823, 2023.
Moderator of the press conference at the 2023 International Conference on Surgical Cancer Care, Callisia N. Clarke, MD, MS, FACS, FSSO, Assistant Professor of Surgery at the Medical College of Wisconsin, highlighted the significance of the 80% response rates to neoadjuvant immunotherapy in primary...