Skin cancer patients appear to fare better if they receive immunotherapy before their cancers are surgically removed, a pair of clinical trials show.
In fact, some do so well that their immune system essentially dissolves their tumors, potentially removing the need for surgery, researchers said.
About half of skin cancer patients who received the immunotherapy drug cemiplimab (Libtayo) had a complete response to the medication, meaning doctors could find no cancer cells left at the tumor site following the advance treatment, according to one of the clinical trials.
Additionally, two patients were able to keep an eye because advance immunotherapy reduced the tumor size and allowed for less extensive surgery, said lead researcher Dr. Neil Gross, a head and neck surgeon with the University of Texas MD Anderson Cancer Center, in Houston.
"Standard treatment would require removing the eye as part of surgery, and then also radiation," Gross said. "These patients responded to immunotherapy, and we able to avoid the devastating consequences of that treatment."
Meanwhile, patients with advanced melanomas experienced a significant improvement in their cancer-free survival if they got the immunotherapy drug pembrolizumab (Keytruda) prior to surgery, according to the second clinical trial, which was funded by the drug's manufacturer Merck & Co.
"These are exciting results," said Marc Hurlbert, CEO of the Melanoma Research Alliance. "I think it does set the stage to the point where in some patients you might be able to de-escalate treatment, meaning in some patients you might be able to avoid surgery. Similarly, maybe we could dial down the need for immunotherapy or dial up the need, depending on how the patient is responding prior to surgery."
Immunotherapy typically is given to patients whose skin cancer has spread to other parts of their body. It's also given to patients after successful cancer treatment, as a means of preventing the cancer from coming back.
These medicines "take the brakes off" the immune system, prompting it to attack cancer cells more vigorously.
Unlocking immune system before tumor removal
"It unlocks the body's immune defenses to treat the cancer, and it turns out that works exceptionally well for cancers that are caused by sun damage," Gross said.
The idea behind these studies is that by leaving the tumor fully in place, doctors are giving the amped-up immune system a bigger target to attack, said Dr. Sapna Patel, lead researcher for the pembrolizumab study and director of the Uveal Melanoma Program at the University of Texas MD Anderson Cancer Center.
"Giving immunotherapy while a tumor is in place generates a stronger and more durable immune response than taking out the tumor and then trying to use immunotherapy," Patel said.
For the first study, Gross and his colleagues recruited 79 people in the United States, Australia and Europe with moderate to advanced cutaneous squamous-cell carcinoma (CSCC). All patients were given up to four doses of cemiplimab prior to surgery and radiation therapy.
About 1 million Americans are diagnosed with CSCC each year, making it one of the most common forms of cancer. Most cases are easily treated by a dermatologist or primary care doctor, and don't need advanced cancer care.
But many of these skin cancers surface around the head and neck, and can affect the eyes, ears, nose and mouth in the rare instances where they spread aggressively.
But cemiplimab completely dissolved the tumors of a little more than 50% of patients, results showed.
Another nearly 13% of patients had a major response to the drug, with their tumors reduced to less than 10% of their original size by surgery time, the researchers said.
For the second study, Patel and her research team recruited 345 patients with operable later-stage melanoma.
All patients were given 18 doses of pembrolizumab, but half received three doses prior to surgery and the rest afterward. The other half received all doses after surgery, which is standard procedure.
"It was the exact same treatment, but simply sequenced slightly differently," Patel explained.
Treatment may be best for those with advanced disease
Patients who received some immunotherapy up front had a 42% lower rate of disease progression, melanoma recurrence or death from any cause at an average follow up of nearly 15 months.
After two years' follow-up, 72% of the people with advance immunotherapy remained event-free compared with 49% of the standard care group, Patel said.
Both drugs are approved by the U.S. Food and Drug Administration, but neither are approved for use prior to surgery in skin cancer patients, the doctors said.
Both teams plan to submit data to the FDA to expand the use of the medications so they can be administered before surgery.
"I could foresee this being offered to patients who have really advanced disease, where the standard treatment would be devastating," Gross said. "Even off-label, I could see that happening."
However, it's too soon to say that using these drugs early in skin cancer treatment could eliminate the need for surgery, said Dr. Alexander Meves, a dermatologist with the Mayo Clinic Comprehensive Cancer Center, in Rochester, Minn.
"Despite the excitement of immunotherapy drugs like cemiplimab, surgery still is important for skin cancer treatment," Meves said.
"Immunotherapy also can have significant adverse effects, including a rare chance of death. Despite only administering four doses of the drug to patients in the [cemiplimab] study, the rate of severe adverse events was 17.7%, which is significant," Meves explained.
"This goes to show that patient selection needs to be done carefully. Immunotherapy is not a good treatment choice for every patient with CSCC, and the risk/benefit over surgery needs to be carefully considered," Meves concluded.
Both studies were presented at the European Society for Medical Oncology annual meeting in Paris. The cemiplimab study, which was funded by Regeneron Pharmaceuticals and Sanofi, was also published Sept. 12 in the New England Journal of Medicine. Findings presented at medical meetings are considered preliminary until published in a peer-reviewed journal.