UConn Health patients with advanced melanoma are benefiting from the same drug credited recently for the disappearance of the disease in former President Jimmy Carter.
Physicians with the Carole and Ray Neag Comprehensive Cancer Center at UConn Health are successfully boosting the immune system of some of their advanced melanoma patients by using a new and promising immunotherapy tool called Keytruda (pembrolizumab) to help them fight the aggressive disease.
The drug was granted accelerated FDA approval in September 2014 for the treatment of advanced melanoma patients who no longer respond to other drug treatments and are not candidates for surgery.
Melanoma is one of the most dangerous and deadly types of skin cancer. If not detected early and removed from the skin, it can spread deep into the skin and to the body’s other organs, such as the lungs, liver, and brain. After melanoma spreads to other organs, chemotherapy treatment is often ineffective and the cancer too complex to be surgically removed. As a result, it is often fatal.
“Melanoma affects the young and the old, and its incidence is on the rise,” says Dr. Upendra P. Hegde, associate professor in the Department of Medicine and chief medical oncologist for melanoma and cutaneous oncology and head and neck cancer/oral oncology at UConn Health’s Neag Comprehensive Cancer Center. More than 75,000 are diagnosed with melanoma annually, and nearly 10,000 Americans die from it each year. In fact, data shows that one person in the U.S. dies from melanoma every 57 minutes.
Hegde says melanoma is often able to spread quickly throughout a person’s body because the immune system gets exhausted. The immune system’s T-lymphocyte cells are the body’s key defenders against traveling cancer cells. Tumors such as melanoma often evade the immune system’s attack by compromising the ability of its T-cells to fight cancer. The tumors do this by expressing a protein called PD-L1 and PD-L2 (program death ligand 1 and 2). These ligands lure T-cells to bind it by expressing on their surface PD-1 receptors. This results in the exhaustion of T-cells and loss of their efficacy to fight tumors.
“This causes the melanoma tumor to start to win the battle, and the immune system to lose, leading to melanoma’s spread,” says Hegde.
However, cancer experts are gaining greater understanding of melanoma and are now using the drug Keytruda as a line of defense to boost a patient’s immune system, helping it fight back and preventing the immune system cells from becoming exhausted. Scientists have successfully blocked PD-1 receptors or their ligands via specific monoclonal antibodies that improve efficacy and extend the life of T-cells to effectively destroy the tumors. Keytruda is one such molecule that the FDA has approved for treating patients diagnosed with metastatic melanoma.
“Keytruda is the first PD-1 inhibitor drug that is allowing us to shrink the melanoma tumors in up to 35 percent of our UConn Health patients,” says Hegde, “and we are continuing to see more progress over time.”
90-Year-Old Man from Harwinton, Conn. Now Cancer-Free
Francis Whalen, 90, of Harwinton, Conn. was one of UConn Health’s first advanced melanoma patients to be prescribed Keytruda, right after it was FDA-approved. As a result, he has had a complete response to the drug therapy.
“My melanoma developed on the top of my scalp and blossomed into a lot of bumps under my skin, on my neck, and also my throat,” says Whalen. “Doctors operated and got some of it, but couldn’t get it all.”
After trying several medications post-surgery to fight Whalen’s melanoma, Hegde was frustrated but then finally relieved to be able to offer his patient the newly approved immunotherapy drug.
“My cancer disappeared between my third and fifth drug treatment. It was such a difference,” says Whalen. “It was a big load off my mind that it worked. They finally hit upon something that worked and I am so glad.”
Whalen, who has very light-colored skin, says he often used to get sunburn over the years, and thinks that may be the reason for his skin cancer.
Hegde says Whalen’s experience is a success story that brings hope for many older patients who are at increasing odds of being diagnosed with metastatic melanoma.
Young Willimantic, Conn. Woman Fighting Back Against Melanoma
Tyana Lopez of Willimantic, Conn. is only 22 years old and is fighting back against recurrence of advanced melanoma.
She first noticed a mole on her right arm two years ago that started changing in texture and color. “One day it just started bleeding,” says Lopez, who went to a dermatologist to have it examined.
The dermatologist took a biopsy of her mole and a week later told her it was melanoma. “My doctor immediately referred me to UConn Health, and they started to offer me solutions right away,” she says.
Lopez had surgery to remove the melanoma from her skin. At the same time, she had lymph nodes under her arm removed by UConn Health surgeon Dr. Bruce Brenner, as they had tested positively for melanoma, showing that the disease had spread. After her surgery, a PET scan of her body came back clear of her stage III melanoma.
But in March 2015, a follow-up PET scan showed that the melanoma was back. A large tumor mass was now encasing her ovaries, and a biopsy confirmed that it was melanoma.
Her oncologist, Dr. Hegde, turned to the use of Keytruda to help Lopez’s immune system fight back.
“I have had treatments every three weeks since the spring, and after the first four I saw a huge difference in my tumor’s size and there are still no new growths. This is a really good sign that I am very happy about,” says Lopez. “I am now living life the best that I can. I am still able to work and I am looking forward to going back to school. Fingers crossed that I continue to have my tumor shrink.”
She says the drug isn’t like typical chemotherapy. “I don’t have to stop doing much in my daily life,” she says. “Also, I have been able to keep my hair and it’s a fun color right now.”
Lopez urges other young people and those of any age to be proactive with their skin health, practicing sun safety and not going tanning or to tanning parlors. She also recommends that everyone become familiar with their skin, know the importance of recognizing any skin changes, and be comfortable going to the dermatologist for screening.
Large Melanoma Tumor of Rocky Hill, Conn. Woman Shrinking
Catherine Pillsbury, 67, of Rocky Hill, Conn. noticed a spot on her cheek in 2013. It was unevenly shaped, had some changes in texture, and it was a few different colors.
She went to a dermatologist and the biopsy of her skin showed it was a melanoma.
Surgery in June 2013 removed it from her cheek. But her oncologist, Dr. Hegde, was concerned, since the melanoma had grown deep into her skin. Doctors continued to closely monitor her every three months.
In May 2015, a follow-up PET scan of Pillsbury’s body showed that an 8 cm tumor had developed in her abdomen. A biopsy confirmed it was also melanoma and linked it to the cancer she had previously had on her cheek.
“I was so impressed that everyone at UConn Health was working together to help figure out the best treatment for my melanoma reoccurrence,” she says.
On June 29, she started receiving the drug Keytruda.
“I am happy that I had the option to try this immunological drug instead of standard chemotherapy that just kills off cells in the body,” Pillsbury says. “Keytruda works by boosting my own immune system.”
After four infusions, the results of her PET scan show that the tumor has shrunk to 2.5 cm. “My doctors are successfully targeting my tumor and it is working,” she says.
She encourages anyone who notices a suspicious mark on their skin to get it checked out.
“If I hadn’t been persistent with my health care, my melanoma could have spread deeper and further,” she says. “Everyone needs to get their skin screened by a dermatologist annually. It could save your life.”
Further Research Investigations
Since not all advanced melanoma patients respond to current available drug therapies or even the immunotherapy Keytruda, researchers at UConn Health’s Neag Comprehensive Cancer Center are exploring the promise of other potential therapy options in clinical trials.
UConn Health is one of two institutions in the Northeast participating in a national 20-site clinical trial called INCYTE. Dr. Jeffrey Wasser is the principal investigator leading this clinical trial at UConn Health. The clinical trial is testing the efficacy of combining Keytruda with another immunotherapy drug known as an IDO1 inhibitor (INCB024360) to see if together these drugs can work to enhance the immune system’s response to fight advanced melanoma, as well as other solid-tumor cancers including lung, triple-negative breast, bladder, ovarian, and other cancers.
UConn Health is also participating in another national clinical trial (MK3475-048-043) testing the possible benefits of the drug Keytruda alone or with standard chemotherapy for patients experiencing a recurrence of head and neck cancer. According to UConn Health principal investigator Dr. Hegde, new therapy options for head and neck cancers are critical, since the conditions are difficult to treat and survival from a recurrence is currently less than 10 percent.
UConn Health’s multidisciplinary melanoma team includes Drs. Jane Grant-Kels and Philip Kerr of Dermatology, Dr. Hegde of Medical Oncology, and Dr. Bruce Brenner, a surgeon who specializes in melanoma, among others.
For more information about the Neag Comprehensive Cancer Center at UConn Health or its clinical trials visit: http://cancer.uchc.edu/.
