For the good news - continued success with the combination therapy. News of this has hit the press from the ASCO conference.
Glaxo
Melanoma Drugs Beat Standard Chemotherapy In Study
BLOOMBERG - By
Makiko Kitamura and Robert Langreth - Jun 4, 2012 12:00 AM ET
Two experimental
GlaxoSmithKline Plc (GSK) drugs that block genes tied to lethal skin cancer
worked better than chemotherapy in studies that tested them individually,
paving the way for final-phase trials on their use together.
About 80 percent of
patients with advanced melanoma given Glaxo’s trametinib were alive after six
months, compared with 67 percent on chemotherapy used as a standard treatment.
Separately, Glaxo’s dabrafenib delayed disease progression by 5.1 months,
compared with 2.7 months for chemotherapy. The Glaxo-funded research is being
reported today at the American Society of Clinical Oncology meeting in Chicago.
The individual research
followed an early-stage study in 77 patients that found the drugs used together
resulted in fewer skin lesions than previously reported with Roche Holding AG
(ROG)’s Zelboraf, a therapy cleared last year that targets a mutant gene found
in half of advanced melanoma cases. Glaxo has begun two final-stage trials on
the combo therapy, the company said.
The combination “is where
we have the most enthusiasm right now,” said Keith Flaherty, director for
developmental cancer therapeutics at Massachusetts General Hospital in Boston,
and an author on the trametinib study. It “looks better in terms of efficacy,
and better in terms of safety.”
The U.S. will have an
estimated 76,250 new cases of melanoma this year, with 9,180 deaths, according
to the National Cancer Institute. While patients with early-stage disease
respond well to treatment, the five-year survival rate for those with cancer
that has spread is 15 percent, according to the American Cancer Society.
Billion-Dollar Drugs
Approval of the two Glaxo
drugs could generate as much as 1.5 billion pounds ($2.35 billion) in 2020,
said Andrew Baum, a London-based analyst at Citigroup Inc., said in a note to
investors last week. The company will seek regulatory approval of both
compounds individually later this year.
In an interview, Paolo
Paoletti, president of the oncology unit for London-based Glaxo, said his
company has begun two late-stage trials of the combination therapy in advanced
skin cancer. One will compare the combination to dabrafenib alone; the other
compares the combo to Roche’s Zelboraf.
“We are rolling; the
interest is so great the enrollment will be very quick,” said Paoletti. If the
benefits of teaming the two drugs hold up, “it is a transformation. It will be
a new standard of care.”
Zelboraf and Glaxo’s
dabrafenib work by blocking BRAF, a mutant gene that spurs cancer cell growth
in about half of melanoma patients. Zelboraf was approved in the U.S. in August
2011. Trametinib is designed to thwart a related protein called MEK that helps
tumors resist an assault on BRAF.
‘Gold Standard’
With few side
effects, the combination therapy could become the industry “gold standard” in
treating melanoma patients with the BRAF mutation as early as 2014, CitiGroup’s
Baum said.
One downside of the
BRAF-blocking drugs is that using them may activate certain growth pathways in
healthy cells, leading to non-melanoma skin cancers. Adding the MEK drug can
block the formation of these skin lesions, it turns out, Flaherty said.
Finding out that a second
drug can cancel out the side effects of the first “was the cool part,” Glaxo’s
Paoletti said. “Usually, when you combine two drugs they increase toxicity.”
Glaxo’s move into
combination trials was “so gutsy,” said George Demetri, an oncologist at Dana
Farber Cancer-Institute in Boston. “Glaxo did a spectacular job.” Demetri said
he was a scientific adviser for one of Roche’s partners in the development of
Zelboraf.
