SOURCES: Jedd Wolchok, M.D., Ph.D., chief, Melanoma and Immunotherapeutics Service, Memorial Sloan Kettering Cancer Center, New York City; Steven O'Day, M.D., director, Los Angeles Skin Cancer Institute; Jyoti Patel, M.D., associate professor, hematology/oncology, Northwestern University Feinberg School of Medicine, Chicago; May 31, 2015, presentation, American Society of Clinical Oncology annual meeting, Chicago; May 31, 2015, New England Journal of Medicine
SUNDAY, May 31, 2015 (HealthDay News) -- The life expectancies of people with advanced melanoma may be doubled or even quadrupled, thanks to a new drug that harnesses the power of patients' immune systems to fight their cancer, researchers reported Sunday.
The drug, nivolumab (Opdivo), slowed cancer progression in melanoma patients by more than double, compared with an earlier immunotherapy drug called ipilimumab (Yervoy).
What's more, the delay in cancer progression nearly quadrupled when the two drugs were combined, compared with taking ipilimumab alone, the researchers said.
But the combination therapy came with greater side effects, which may limit treatment in frail patients. However, the researchers noted that no deaths occurred during the large-scale, international clinical trial.
"This trial was conducted at 137 sites globally, and the safety guidelines that were in place clearly were able to handle these side effects," said study author Dr. Jedd Wolchok, chief of the Melanoma and Immunotherapeutics Service at Memorial Sloan Kettering Cancer Center in New York City. "This treatment can be safely applied in a global setting."
The findings were presented Sunday at the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago; they were published simultaneously in the New England Journal of Medicine.
Nivolumab and ipilimumab both belong to a class of drugs called immune checkpoint inhibitors, which boost the immune system's ability to attack and destroy cancer cells, the researchers explained.
Cancer cells flout immune attack by hiding behind processes that normally keep the immune system from running amok and targeting healthy cells.
Ipilimumab works by blocking a "switch" called CTLA-4 that cancer cells use to masquerade as normal cells. It was the first drug to be associated with an improvement in overall survival for patients with advanced melanoma, the researchers said in background information.
But nivolumab belongs to a second-generation set of immune checkpoint inhibitors that target a more cancer-specific "switch" called PD1. Another study presented earlier at the ASCO meeting showed that nivolumab is effective in treating lung cancer as well.
Both ipilimumab and nivolumab are FDA-approved for use in patients with melanoma that is advanced or cannot be removed by surgery.
To compare the effectiveness of the two drugs, the researchers randomly assigned 945 patients with previously untreated, advanced melanoma to receive ipilimumab, nivolumab or a combination of the two.
They found that nivolumab alone more than doubled the average time to disease progression, compared to ipilimumab -- almost 7 months versus almost 3 months.
Patients did even better when ipilimumab and nivolumab were combined, receiving an average delay of 11.5 months before their disease progressed.
More patients also responded to therapy that included nivolumab. About 57 percent responded to the combination therapy, compared with 43 percent for nivolumab alone and 19 percent for ipilimumab.
Nivolumab also did a better job of shrinking patients' tumors. The average patient experienced a 52 percent reduction in cancerous tissue with the combination therapy and a 34 percent reduction with nivolumab alone. On the other hand, patients treated with ipilimumab alone experienced only a 6 percent decrease in tumor size, the researchers said.
People responded best to nivolumab if their cancers contained a molecule called PD-L1, which is the means by which the tumors exploit the PD-1 "switch" to avoid detection by the immune system, the researchers found.
In fact, patients with PD-L1-positive tumors responded just as well to nivolumab alone as they did to the combination therapy, the study found.
On the other hand, those with tumors that had low levels of PD-L1 responded best to the combination therapy.
Using these drugs to unleash the immune system can cause other health problems, and the most common side effects in this study were diarrhea, rash, fatigue, itching and nausea.
About 36 percent of patients receiving the combination therapy had to drop out of the trial due to side effects, compared with about 8 percent for nivolumab and 15 percent for ipilimumab, the researchers said.
"The nivolumab and ipilimumab combination in this study came with greater side effects, which might offset its benefits for some patients," said melanoma expert Dr. Steven O'Day, director of the Los Angeles Skin Cancer Institute. "Physicians and patients will need to weigh these considerations carefully."
However, O'Day noted that 68 percent of patients who dropped out due to side effects ended up responding to the combination therapy, and half responded after the therapy had been suspended.
ASCO spokesperson Dr. Jyoti Patel said that doctors likely will be able to use the PD-L1 molecule to help detect patients who will benefit from nivolumab alone, so they won't have to endure the side effects of the combo therapy.
"We are beginning to define which patients may benefit from one drug and which patients may benefit from multiple drugs," said Patel, an associate professor of hematology/oncology at Northwestern University Feinberg School of Medicine in Chicago.
The study was funded by the drug's manufacturer, Bristol-Myers Squibb.
Visit the U.S. National Institutes of Health for more on melanoma.