Dr. Antoni Ribas (far right) with members of his research team at UCLA, who helped lead the clinical trial showing that immunotherapy before surgery can shrink or eliminate tumors in patients with desmoplastic melanoma.
Photo Credit: Courtesy of UCLA/Health
Scientific Frontline: "At a Glance" Summary
- Main Discovery: Neoadjuvant treatment with the immunotherapy drug pembrolizumab significantly shrinks or eliminates tumors in patients with desmoplastic melanoma, a rare and aggressive form of skin cancer.
- Methodology: In the SWOG S1512 clinical trial (Cohort A), researchers administered three infusions of pembrolizumab over a nine-week period to 28 patients with surgically resectable desmoplastic melanoma prior to their scheduled surgery.
- Key Data: Pathologic analysis revealed that 71% of patients had no detectable live tumor cells at the time of surgery, and at the three-year follow-up, 95% of patients survived with a 74% disease-free recurrence rate.
- Significance: This therapeutic approach can spare patients from extensive, potentially disfiguring surgeries and postoperative radiation, drastically improving quality of life without compromising survival outcomes.
- Future Application: The findings support a paradigm shift toward using PD-1 blockade immunotherapy as the standard neoadjuvant care for resectable desmoplastic melanoma, replacing immediate invasive excision.
- Branch of Science: Oncology, Immunology, and Dermatology.
- Additional Detail: Desmoplastic melanoma, typically resistant to chemotherapy and radiation, was found to be highly responsive to PD-1 blockade due to its high mutational burden caused by UV damage.
New results from a clinical trial co-led by UCLA investigators demonstrate how treating desmoplastic melanoma, a rare and aggressive skin cancer, with immunotherapy before surgery can dramatically shrink or even eliminate tumors, sparing patients from more aggressive surgeries and preserving their quality of life.
The findings published in Nature Cancer, show that 71% of patients who received the immunotherapy drug pembrolizumab, an anti-PD-1 immune checkpoint inhibitor that stimulates the body’s immune system to fight cancer, before surgery had no detectable cancer remaining at the time of surgery.
The multicenter clinical trial, known as SWOG S1512, was conducted by the SWOG Cancer Research Network and funded by the National Cancer Institute. It marks the first study to test neoadjuvant PD-1 blockade in this population and suggests a promising new treatment approach.
“We’re seeing that desmoplastic melanoma, which can be challenging to remove surgically, responds extremely well to immunotherapy,” said Dr. Antoni Ribas, the study’s senior author, a professor of medicine at the David Geffen School of Medicine at UCLA and director of the UCLA Health Jonsson Comprehensive Cancer Center’s Tumor Immunology Program. “We found that giving pembrolizumab before surgery is a powerful and safe approach that reduces the need for invasive procedures and improves long-term outcomes.”
Desmoplastic melanoma often develops on sun-exposed areas of skin, such as the head and neck, and grows deep into tissues, sometimes along nerves, making surgery challenging and potentially disfiguring. Historically, wide surgical excision followed by radiation has been the standard approach, while advanced disease was considered largely resistant to systemic therapies such as chemotherapy or immunotherapy.
Building on earlier findings from cohort B of SWOG S1512, which showed that pembrolizumab shrank tumors in nearly 90% of patients with advanced, inoperable desmoplastic melanoma, the current study explored whether the therapy could also benefit patients with surgically removable tumors.
In this group of patients, known as cohort A, 28 patients with surgically resectable desmoplastic melanoma received three infusions of pembrolizumab over nine weeks prior to surgery. Researchers collected tissue samples before, during and after therapy to track tumor response.
The team found that the treatment resulted in a high response rate, with 71% of patients receiving pembrolizumab having no detectable cancer at the time of surgery, and side effects were generally mild.
At the three-year follow-up, 95% of patients had not died from the disease, and 74% remained cancer-free.
“Giving pembrolizumab before surgery led to very high rates of tumor clearance, few serious side effects, and excellent three-year survival for patients with this rare and difficult-to-treat cancer,” said Ribas, who is also director of the Parker Institute for Cancer Immunotherapy Center at UCLA and a member of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA. “Taken together with our earlier findings in patients with advanced disease, these results represent a true shift in how desmoplastic melanoma is treated, moving away from repeated surgeries and radiation toward a single therapy that offers durable control, improved survival, and better quality of life.”
Funding: The study was funded by grants from SWOG, National Institutes of Health and the National Cancer Institute.
Published in journal: Nature Cancer
Authors: Kari L. Kendra, Shay L. Bellasea, Zeynep Eroglu, Siwen Hu-Lieskovan, Katie M. Campbell, William E. Carson III, David A. Wada, Jose A. Plaza, Gino K. In, Alexandra Ikeguchi, John Hyngstrom, Andrew S. Brohl, Bartosz Chmielowski, Nikhil I. Khushalani, Joseph Markowitz, Marcus Monroe, Carlo M. Contreras, Tawnya Bowles, Kurt Norman, Egmidio Medina, Cynthia R. Gonzalez, Ignacio Baselga-Carretero, Ivan Perez Garcilazo, Agustin Vega-Crespo, Jia Ming Chen, Nataly Naser Al Deen, Sapna P. Patel, Kenneth F. Grossmann, Vernon K. Sondak, Elad Sharon, James Moon, Michael C. Wu, and Antoni Ribas
Source/Credit: University of California, Los Angeles / Health | Denise Heady
Reference Number: ongy012926_01