Adding a white-blood cell boosting treatment from Sanofi to Bristol-Myers Squibb Co.’s melanoma drug Yervoy helped patients with advanced skin cancer live longer and lessened side effects, a study found.
In the trial of 245 patients led by researchers at the Dana-Farber Cancer Institute in Boston, 68.9 percent of patients who got Yervoy, designed to spur the immune system to attack cancer cells, and the Sanofi drug, GM-CSF, were alive one year later, compared to 52.9 percent of those who got Yervoy alone.
The results, presented at the American Society of Clinical Oncology meeting, show that two immune-stimulating drugs may be better than one in treating melanoma, the most deadly form of skin cancer. While the finding needs to be confirmed in a larger study before the combination is routinely practiced, it offers a first, hopeful glimpse into a potential new approach for battling the disease that kills 9,500 people each year.
“It is very interesting and promising new data,” said Jedd Wolchok, an oncologist at Memorial Sloan-Kettering Cancer Center in New York, who was not involved in the study. “I do think the effect is real.”
The finding is also the latest in a series of positive news for patients with advanced melanoma. In 2011, Yervoy became the first drug proven to boost survival in the disease. In May, two more drugs for advanced melanoma from GlaxoSmithKline Plc were approved by U.S. regulators. At the oncology conference today, researchers are presenting a study showing that the experimental drug selumetinib from AstraZeneca Plc may help treat eye melanoma, a particularly treatment-resistant form.
GM-CSF is a white blood cell stimulant that is sold under the brand name Leukine by Sanofi and used for rejuvenating white blood cells after bone marrow transplants or high-dose chemotherapy. The new trial was based on animal studies indicating that adding GM-CSF to Yervoy creates a synergistic effect, said study leader Stephen Hodi, director of the melanoma center at Dana-Farber Cancer Institute and an associate professor of medicine at Harvard Medical School.
While both drugs are on the market and could be used together by oncologists now, how to translate the result into everyday practice isn’t clear because the study used a much higher dose of Yervoy than is currently approved.
Nonetheless, “I don’t think there is a downside” to considering the combination, Hodi said in a phone interview. “Certainly there is potential for improved efficacy and an improved safety profile.”
Doctors aren’t sure why patients who got the combination lived longer, as the combination therapy didn’t result in a higher rate of major tumor shrinkage or delay progression of the disease. Adding the second drug may reduce life threatening immune-related side effects that occur with Yervoy, such as colon inflammation, said Hodi.
Patients in the trial who got the combination had less gastrointestinal and lung toxicity, Hodi said. Two patients taking the combination died of treatment related side-effects, versus seven patients who received Yervoy alone who died of possible treatment side-effects.
The results “add to our understanding” of how to combine immune-based therapies, said Michael Giordano, a senior vice president for New York-based Bristol-Myers in an e-mailed statement. “We will collaborate with the authors to better understand these results.”
Just under 77,000 Americans develop melanoma each year, and almost 9,500 patients die from the disease, according to the American Cancer Society. While most cases are caught at an early stage, the disease can be rapidly fatal once it spreads beyond the skin.
In a separate 98-patient study presented at the meeting, researchers from Memorial-Sloan Kettering Cancer Center in New York reported that selumetinib, an experimental drug from AstraZeneca, delayed progression of eye melanoma, or uveal melanoma, by about two months compared to chemotherapy.
Patients who got the experimental drug lived nearly four months before their disease spread further, compared to less than two months for those who received chemotherapy. The trial didn’t find a statistically significant difference in survival, which was a median of 10.8 months for patients who got the AstraZeneca drug and 9.4 months for those who got chemotherapy.
While the improvement is modest, it represents an important starting point as there are no approved treatments for the rare eye disease, said Richard Carvajal, an oncologist at Memorial Sloan-Kettering Cancer Center who led the study. In eight previous trials of various agents on 157 eye melanoma patients, only 2 eye melanoma patients had experienced tumor shrinkage, he said in a phone interview.
The eye disease affects 2,000 to 2,500 Americans each year, said Carvajal.
“Showing any efficacy in uveal melanoma is a tremendous step forward because there is basically nothing now,” said Hodi in a phone interview.
In an e-mailed statement, AstraZeneca vice president Donna Francher said the findings “are encouraging and demonstrate the need for further study in this population.”