Melanoma is a deadly form of skin cancer because it has the ability to metastasize (spread) to many sites, including the brain, lungs, and liver. On September 4, the Food and Drug Administration (FDA) approved Keytruda (pembrolizumab) for the treatment of melanoma following the results of a clinical study led by UCLA researchers. The drug has been termed a “game changer” by principal author Dr. Antoni Ribas, a professor of medicine in the division of hematology–oncology at the David Geffen School of Medicine at UCLA. In addition to UCLA, the research was conducted at 10 other sites in the US, Europe, and Australia.
Keytruda was tested on more than 600 melanoma patients who metastatic disease throughout their bodies. During the early testing, many of the patients had significant long-lasting responses; therefore, the study was continued and the FDA granted the drug “breakthrough therapy” status, which allowed it to be fast-tracked for approval.
Keytruda is an antibody that targets a protein known as PD-1, which is expressed by immune cells. The protein inhibits the immune system by preventing its T cells from recognizing and attacking cancer cells, explained Dr. Antoni Ribas. He said, “For patients who have not responded to prior therapies, this drug now provides a very real chance to shrink their tumors and the hope of a lasting response to treatment.”
For a number of years, when using immunotherapy to fight cancer, the strategy has been to boost the immune system so that it could kill the cancer cells. However, the method has had limited success because PD-1 prevented the immune system from becoming active enough to attack the cancer. The drug stimulates the immune system to a level in which in can attack the malignancy.
Judith Gasson, senior associate dean for research at the David Geffen School of Medicine at UCLA and director of UCLA’s Jonsson Comprehensive Cancer Center, noted that scientists have long hoped to develop an effective and lasting immunotherapy to fight cancer. She explained, “We have long believed that harnessing the power of our own immune systems would dramatically alter cancer treatment. Based upon work conducted over the past two decades, we are beginning to see the clinical benefits of this research in some of the most challenging cancers.”
As a rule, approximately 1 in 10 patients respond to previous immunotherapy drugs. However, some of those who responded, however, exhibited long-lasting benefits, which sustained researchers’ interest in the method as an effective mechanism to fight cancer. Dr. Ribas noted that the response and duration rates for Keytruda were much greater than for previous drugs, Ribas noted. In the new study, 72% of the patients responded to the drug and their tumors decreased in size. Overall, 34% of patients showed a measurable response; their tumors shrank by more than 30%, and did not re-grow. Dr. Ribas said that Keytruda has the potential to be used to treat other cancers that the immune system can recognize, including cancers of the lung, bladder, head and neck.
Two survivors’ stories:
Kathy Thomas, 59, of Torrance, California, was diagnosed in September 2011 with melanoma that had spread to her liver and was invading her left breast. She underwent several rounds of treatment that were unsuccessful and her condition was worsening. “I lost weight. I threw up nearly every day,” Ms. Thomas said, adding, “My hair was thinning. I just had no strength at all. I was so sick I had to use a wheelchair.” In 2013, Ms. Thomas met with Dr. Ribas in 2012. She was initially skeptical of the therapy; however, she overcame her hesitation. She explained, “I decided I wanted to survive. I wasn’t going to let this disease beat me.”
Since her enrollment in the study, the tumors have shrunk. She has regained her strength and her appetite. She is out of her wheelchair and walking normally again. In addition, she experienced no side-effects from the treatment, and she travels monthly to San Francisco to visit her grandson. “I just enjoy life now, really enjoy it,” she said.
Tom Stutz, 74, of Sherman Oaks, California, was diagnosed in June 2011 with melanoma that had spread to his lung, liver, and other areas. He felt his condition was hopeless; however, he decided to enroll in the clinical trial anyway. He explained, “I wasn’t eating. I was on oxygen. I couldn’t walk. When I went into the hospital at the end of May , I didn’t think I was coming out.” However, Mr. Stutz soon started feeling better. Today, he is no longer on oxygen and walks several miles every day.
He said, “It’s the little things that make me happy now. I’m very appreciative that I get to get up in the morning, go into my backyard, and see my garden. I’m able to be with my children and grandchildren, go on vacations with them. I was close to the end of the road, as far as you can get to the edge of the cliff, and I was pulled back by this treatment.”
For the past three decades, the incidence of melanoma has been increasing. In the US in 2014, an estimated 76,100 new cases of melanoma will be diagnosed, and nearly 10,000 Americans will die from the disease this year. According to the American Cancer Society, melanoma accounts for less than 2% of all skin cancer cases; however, it is responsible for the vast majority of skin cancer deaths.
For more information about Keytruda clinical trials at UCLA, members of the public are invited to call 888-798-0719.