| June 2
June 2 New data on Bristol-Myers Squibb Co's
melanoma drug Yervoy, including fresh results from an
effort to combine it with another promising cancer
immunotherapy, suggest it can improve treatment for patients
with both advanced and slightly earlier stage disease, according
to findings released on Monday.
Yervoy, which takes natural brakes off the immune system to
help it more effectively attack cancer, is approved to treat
metastatic, or stage 4, melanoma - the deadliest form of skin
cancer. Cowen and Co expects the drug to capture annual sales of
$1.95 billion by 2020, as it is approved in new indications and
combinations with other treatments.
During the annual American Society of Clinical Oncology
meeting in Chicago, Bristol-Myers presented several studies on
Yervoy and nivolumab, its experimental cancer immunotherapy from
a highly promising class called PD-1 inhibitors, both as
standalone treatments and in combination.
In one late-stage study on Yervoy alone, the drug reduced
the risk of melanoma recurrence by 25 percent following surgery
compared with a placebo. The median recurrence-free survival
(RFS), or average time to disease return, following successful
surgery to remove cancerous tumors was 26.1 months for Yervoy
compared with 17.1 months for the placebo group. The result was
deemed to be statistically significant.
Patients in this study had stage 3 disease in which the
cancer had spread to regional lymph nodes but not yet to other
parts of the body.
"This benefit was observed across all patient sub-groups,
including those who were at highest risk of recurrence,"
Alexander Eggermont, the study's lead investigator, said in a
The result could pave the way for the drug's use earlier in
the disease and boost future sales. Current treatment options to
reduce the risk of recurrence following surgery are very
limited, Eggermont said.
The 951-patient Phase III study was the first large trial to
look at Yervoy's effect following complete resection surgery.
Overall survival data was not yet available. But three years
after beginning treatment, an estimated 46.5 percent of Yervoy
patients were free of disease recurrence compared with 34.8
percent in the placebo group.
Nearly half of the Yervoy patients stopped treatment due to
side effects, which are common with the drug, and there were
five drug-related deaths, or 1.1 percent, researchers reported.
Ron Peck, Bristol's global development leader for Yervoy,
said a high 10 milligram dose was used in the study and may have
contributed to the side effect rate. A 3 mg dose is being used
in later studies.
LONG-TERM SURVIVAL FOR COMBINATION
Data from a separate, early-stage study of advanced melanoma
patients showed results for Yervoy combined with nivolumab that
researchers found very encouraging.
At two years, the overall survival rate for the first 53
patients in the study was estimated to be 79 percent, down only
a bit from the 85 percent survival rate reported after one year.
"If this survival data is confirmed in Phase III trials,
it's unprecedented. This is really exciting data," said Dr.
Mario Sznol, a professor of medicine at Yale Cancer Center in
New Haven, Connecticut, and the study's lead investigator.
Having 80 percent of advanced melanoma patients alive at two
years "is almost unheard of," Sznol said in a telephone
Among the 17 patients in the study who received the two drug
doses that Bristol chose to test in its larger, later stage
trials the two-year survival rate was 88 percent.
Seventeen percent of patients in the study had a complete
response, or no detectable cancer. Sznol expects that number to
rise. Immunotherapy results often improve over time as the
immune system learns to fight the disease.
The results were consistent whether or not a patient's
tumors expressed the PD-L1 protein, which helps camouflage them
against the immune system. Patients who are deemed negative for
PD-L1 tend to get little benefit from drugs like nivolumab
alone, suggesting the addition of Yervoy may also help them.
The incidence of serious side effects among the first 53
patients in the study was about 53 percent and rose to 62
percent with an additional group of 41 more patients. There was
a 23 percent discontinuation rate due to side effects and one
drug-related death, researchers reported.
"These toxicities really are manageable in the clinic,"
Sznol said. "If you're getting 79 percent overall survival at
two years, the side effects are clearly worth it."
(Reporting by Bill Berkrot; Editing by Michele Gershberg and