One of the most gratifying parts of the job for oncologist John Kaczmar, M.D., is being able to offer skin cancer patients the newest treatments that can potentially cure their cancer without requiring surgery, radiation or chemotherapies with disabling side effects.
That’s what happened with Tim Buikema. A clinical trial of two immunotherapy drugs in combination helped his body’s own immune system to take down a melanoma, to the point that PET scans now show no signs of cancer.
Although a similar agent, developed by a different company, received regulatory approval earlier this year to treat advanced melanoma, neither of these medications was publicly available at the time that Buikema needed help.
In fact, the only patients who received the LAG-3 inhibitors like those that Buikema received were those who signed up for clinical trials.
“That is just the most amazing thing, when we can offer patients early access to therapies that have the potential to become standard-of-care,” Kaczmar said.
Buikema, of Gray Court, South Carolina, arrived at MUSC Hollings Cancer Center with a bulging melanoma on his left cheek that was obstructing his vision.
Buikema had previously had a few Mohs surgeries to remove nodules and growths. But when his surgeon pointed out a new, small growth in 2018, Buikema was frustrated at the recurring surgeries and decided to try a holistic approach focused on diet, body and mind. Unfortunately, the melanoma continued to grow. Eventually, Buikema was referred to Hollings.
Once at Hollings, the initial treatment plan was surgery – but Buikema refused it. Because of the size of the melanoma, the surgery would have affected most of the left side of his face, including his nose, upper lip and eye, permanently changing his appearance.
“I just knew that I would not live well or long with the complications the surgery suggested, so surgery was not the answer after having prior cancer extractions,” he said.
Clinical trials can be a gamechanger for skin cancer
But one of the benefits of coming to Hollings is the multitude of available clinical trials that seek to improve upon current treatments. And with the surgery option off the table, Buikema met up with Kaczmar to talk about the immunotherapy clinical trial.
Kaczmar said that anti-PD1 drugs have become the backbone of melanoma care. PD-1, or programmed death-1, is a protein found on T-cells, which are part of the body’s immune system. It’s meant to prevent T-cells from attacking the body’s own cells. But many cancer cells have a protein that binds to PD-1 and thus instructs the T-cells that the cancer cells are off limits. Immunotherapy prevents that binding and enables the T-cells to do their job of destroying the cancer cells.
“That’s benefited so many patients, and survival of even the most advanced melanomas has increased a significant amount where we’re seeing many patients who wouldn’t have been alive in the past, now living years and years and sometimes living without cancer,” Kaczmar said.
“This trial is one of those trials looking at adding something else to this anti-PD1 backbone to potentially improve responses and potentially make them more durable.”
Dr. John Kaczmar
Still, some patients don’t respond to the immunotherapy. Some have an initial response, but the cancer returns.
“There’s a lot of interest in improving upon the good backbone that we have,” Kaczmar explained. “And this trial is one of those trials looking at adding something else to this anti-PD1 backbone to potentially improve responses and potentially make them more durable.”
Buikema received anti-PD1 as well as a new agent that targets LAG-3, another immune checkpoint receptor protein.
The study tracked response to the drugs through measurements on scans, but neither Buikema nor the Hollings team needed a scan to see the results.
“We saw it even before the study-mandated imaging. We saw it shrinking before our eyes,” Kaczmar said. “So we knew there was going to be a response. And then, when we obtained imaging per the protocol, we saw it shrinking markedly.”
Kaczmar noted that not all patients responded as well as Buikema. In this trial, he said, more than 60% of patients saw a response.
“Understanding why some people respond to immune therapy and others don’t is still certainly an area of investigation,” he said. “We still struggle with that, but we are learning more and more of the signatures that at least predispose one to a response.”
Immunotherapy and side effects
Another benefit of immunotherapy is the potential for fewer side effects than traditional treatments like chemotherapy. Some patients have no side effects on immunotherapy. Buikema did experience side effects, including inflammation in his lungs, adrenal insufficiency and colitis. However, Kaczmar said, those effects can be treated, and in Buikema’s case, they have since gone into remission. Kaczmar said the potential side effects of immunotherapy are, on average, much more manageable than the side effects of chemotherapy.
“You’re not losing your hair. You’re not having your blood counts go down and being at increased risk for an infection,” he said. “So really, on balance, it is a game-changer for patients. When they can benefit from it, they can really carry on their normal life.”
Buikema said he loves being outside, whether walking in the woods, gardening or playing with his grandsons.
“In hindsight, I should have applied sunscreen daily, as I do now,” he said. “I am so grateful to the Hollings Cancer Center. The level of care I received from the people working there – especially Dr. Kaczmar – has been life-changing.”