An extremely promising area of cancer research is immunotherapy. Instead of chemotherapy that destroys cancerous cells but also damages normal cells, immunotherapy stimulates the body’s own immune system to seek out and destroy malignant cells. In the July edition of The New England Journal of Medicine, researchers at UCLA’s Jonsson Comprehensive Cancer Center reported the promising results of Keytruda (pembrolizumab) for the treatment of malignant metastatic melanoma (skin cancer that had spread to other areas of the body.
A participant of the pembrolizumab clinical trial, Tom Stutz , a retired attorney from Sherman Oaks was facing imminent mortality. Melanoma had metastasized to his lung, liver, spine and shoulder. Fortuitously, he was able to be included in a clinical trial on an experimental immunotherapy therapy drug pembrolizumab, also known as a checkpoint inhibitor. Three years later, he is alive and well with only one small suspicious area in his lung. Stutz was diagnosed with melanoma. One hear later, he was in near death and was confined to a wheelchair and connected to an oxygen tank for what he believed to be his last days on Earth. He recalled, “I had to sleep sitting up and could only get catnaps. I used to dread the night.”
Stutz found renewed hope after meeting with Dr. Antoni Ribas, a professor of medicine, surgery and pharmacology at UCLA; Dr. Ribas enrolled him in one of the last spots in a Phase 1 clinical trial on an experimental drug for advanced melanoma treatment. The study was designed to evaluate the drug’s safety at various doses and to determine its effectiveness.
At present, Stutz enjoys excellent health. He travels, plays tennis, and cycles. In addition, he is not an isolated case of dramatic recovery; rather, he is among a growing number of cancer victims who are being restored to health by state-of-the-art immunotherapy treatments.
Because of the extremely promising results, pembrolizumab, received “fast-track” approval by the Food and Drug Administration (FDA) last fall and now is being prescribed under the brand name Keytruda. It is among the first in a new class of immunotherapies known as checkpoint inhibitors. In December 2014, another drug, nivolumab (Opdivo), was approved by the FDA for metastatic melanoma and, two months later, for patients with metastatic squamous non-small-cell lung cancer. In addition, several other drugs with similar mechanisms of actions are currently under development. Pembrolizumab and nivolumab represent a quantum leap in progress in the field of cancer immunotherapy. Currently, many cancer experts believe immunotherapies will emerge as primary treatment modality for many types of malignancies; furthermore, they may replace many chemotherapy drugs aa the treatment of choice.
“I’ve been working in the field of immunotherapy for lung cancer for 25 years,” explained Dr. Steven M. Dubinett, chief of the Division of Pulmonary and Critical-care Medicine and director of UCLA’s Jonsson Comprehensive Cancer Center’s lung cancer research program. He added, “I think we had all hoped that there would come a point where our knowledge about human immunotherapy would be sufficient to overcome critical obstacles. That has come to pass, and, although many questions remain to be addressed in further research, optimism is certainly warranted.” The checkpoint inhibitors “have been one of the biggest stories in cancer in the last 10 years, and they are the biggest advance in cancer immunotherapy ever,” added Dr. John Timmerman, an associate professor of medicine in the Division of Hematology/Oncology.
When he launched his clinical trial, Dr. Ribas was hopeful that Keytruda drug would be effective in 10-to-15% of patients with advanced melanoma. During his first three weeks of treatment, Stutz did not experience any benefits. He said, “I got quite a lot worse. I couldn’t turn over in bed without being out of breath.” As a result, he had to undergo a thoracentesis, which is a procedure to drain fluid from the lungs. Then, one night, one of his erratic catnaps stretched into a blissful 16 hours of uninterrupted sleep. Gradually, he found he could breathe easier. He took short walks outside his house, adding a few more steps every day. By June, he no longer needed oxygen therapy. In July, a scan showed the two main tumors in his liver and lung had shrunk by 50%.
At present, Stutz still receives Keytruda infusions every three weeks. There is a dark spot in his lung that may be a small tumor, the remnants of a tumor, or scar tissue. Stutz is not concerned with the lesion. He is alive and well, spending quality time with his children and grandchildren. He explained, “In the beginning, I was stunned. I would say to myself: I can’t believe I’m still here. The wonderful thing about this treatment, besides the result, is you can live pretty much a normal life. The side effects are minimal.”
The clinical trial that Stutz enrolled in showed that one-third of patients with advanced melanoma experienced long-term responses to pembrolizumab. Another third had some tumor shrinkage; however, the disease eventually progressed. Only 12% of the subjects had a significant side effect, such as fatigue or joint pain. Dr. Ribas was extremely pleased with the outcome of the trial. He explained, “I honestly didn’t think it would work this well. When we started the clinical trial, sometimes we tried to select patients whom we thought would be more likely to benefit. Then we started giving it to patients with more aggressive metastatic melanoma, even patients who were at the limit of eligibility for the clinical trial, where a day or two more and they wouldn’t have been eligible. Some of those patients responded. Those were patients where, if we didn’t do anything, life expectancy would have been weeks.”
Keytruda therapy also appears to attack cancers that have spread throughout the body, including the brain. “If you get an immunotherapy that works really well, it can work all over,” Dr. Ribas explained. Currently, similar equally promising results are being reported with other checkpoint inhibitors and in other types of cancer. About a third (32%) of melanoma patients receiving nivolumab experienced a reduction in tumor size, and more than one-third experienced an effect that lasted for more than six months. In patients with advanced squamous non-small-cell lung cancer, nivolumab produced tumor shrinkage or the complete disappearance of the tumor in 15% of patients, many with long-lasting results.
In a presentation lar April at the American Association for Cancer Research annual meeting in Philadelphia, Pennsylvania, UCLA researchers reported evidence of positive responses to pembrolizumab in approximately 205 of patients with non-small-cell lung cancer. The study is slated for publication in the New England Journal of Medicine.
