By Peter Loftus
Merck & Co.'s new cancer drug Keytruda improved the survival
odds of patients with the skin cancer melanoma compared with
Bristol-Myers Squibb Co.'s Yervoy, in the first head-to-head study
of a new wave of drugs that harness the body's immune system to
destroy tumors.
As scientists reported the results Sunday at a medical
conference, Merck also said it has filed for U.S. regulatory
approval to market Keytruda as a treatment for lung cancer, which
represents a bigger patient population than melanoma.
Bristol, Merck, Roche Holding AG and other drug makers are
racing for a share of the burgeoning cancer immunotherapy market,
which some analysts predict could reach $20 billion to $30 billion
in annual sales in the next decade.
Both Yervoy and Keytruda are immunotherapies, but they work in
different ways. Yervoy has become the standard first-line treatment
for advanced melanoma since hitting the market in 2011, helping it
to rack up $1.3 billion in sales last year. Keytruda, known as a
PD-1 inhibitor, was approved last year to treat melanoma in
patients whose disease worsened after trying Yervoy.
Yervoy was the first drug to reach the market for advanced
melanoma shown to prolong life. It "became the gold standard
against which everything else had to be measured," said Suzanne
Topalian, director of the melanoma program at Johns Hopkins Kimmel
Cancer Center.
With the new study showing Keytruda superior to Yervoy, "this is
now expected to change the treatment landscape for melanoma," she
said. "This is a high impact trial."
The study reported Sunday tested Keytruda against Yervoy in more
than 830 patients whose melanoma had spread to other parts of the
body. About one-third of patients received Keytruda once every two
weeks, one-third received it every three weeks, and the remaining
one-third received the standard four cycles of Yervoy.
One year after the start of treatment, 74% of patients who
received Keytruda every two weeks and 68% of those who received it
every three weeks were still alive, compared with 58% for those who
received Yervoy. Measured another way, Keytruda reduced the risk of
death by 31% to 37% versus Yervoy, according to the results, which
were published online Sunday by the New England Journal of Medicine
and presented at the annual meeting of the American Association for
Cancer Research in Philadelphia.
The survival benefit prompted an independent monitoring
committee to recommend in March that the study be stopped early so
that patients who received Yervoy could be given the option of
receiving Keytruda. The rates of serious side effects--including
the inflammatory bowel disease colitis--were lower among patients
who took Keytruda than those on Yervoy.
"The treatment paradigm for patients with advanced melanoma
should be changed because a PD-1 antibody up front is beneficial,"
said Antoni Ribas, professor of oncology at UCLA's Jonsson cancer
center, one of the leaders of the Merck-funded study and co-author
of the NEJM paper. "It has a higher response rate and a better
safety profile."
Merck plans around mid-year to apply for regulatory approval of
Keytruda as a first-line treatment for metastatic melanoma. Roger
Perlmutter, president of Merck's research arm, said the new study
supports Keytruda as "the favored drug" in first-line
treatment.
Bristol-Myers' Opdivo acts on the same PD-1 mechanism as
Keytruda. Dr. Ribas said it is likely Opdivo is similarly more
effective against melanoma than Yervoy, though it wasn't tested in
the study reported Sunday.
But Yervoy may not be fully supplanted as a first-line treatment
for metastatic melanoma. Bristol-Myers has been testing a regimen
combining Yervoy with its own anti-PD-1 drug, Opdivo, for
metastatic melanoma. It has shown promising survival benefits in
prior studies, but with relatively high rates of adverse events.
Results of a new study of the combination are due out Monday.
Fouad Namouni, head of Bristol-Myers's development program for
Yervoy and Opdivo, said Yervoy "set a new standard in durable
long-term survival," and the company now believes the future of
melanoma treatment lies in combining immunotherapies including
Yervoy and Opdivo.
In a separate study released Sunday, Keytruda significantly
shrank tumors in 19% of patients with lung cancer in an early-stage
trial. The tumor-shrinkage rate was higher, at 45%, among patients
whose tumors substantially expressed a substance called PD-L1,
which tumor cells use to interact with another substance, PD-1,
which is present on immune cells, to escape destruction. The
results suggest that the level of a tumor's PD-L1 expression could
be used to predict which patients will respond best to drugs that
block the PD-1/PD-L1 interaction, said Edward Garon, a UCLA
oncologist who co-authored the study.
Merck has filed for U.S. regulatory approval of Keytruda to
treat non-small-cell lung cancer.
Earlier this year, Bristol's Opdivo was approved by the Food and
Drug Administration to treat a subtype of non-small cell lung
cancer. On Friday, Bristol said a clinical trial of patients with
another subtype of lung cancer was stopped early because Opdivo
improved survival compared with chemotherapy.
Ron Winslow contributed to this article.
Write to Peter Loftus at peter.loftus@wsj.com
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