[But developing such a
test has proved tricky so far, for ethical as well as scientific reasons. Some
doctors said it would be unfair to withhold the new drugs from patients based
on a test if there was still even a slight chance that the drugs would help.]
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|
Dr.
Jedd D. Wolchok, chief of the melanoma and immunotherapeutics service at
the Memorial
Sloan Kettering Cancer Center. Credit Memorial Sloan Kettering Cancer Center
|
New drugs that boost the immune system’s ability to fight tumors
may be one of the greatest medical advances in years, cancer doctors say, pulling some patients
from death’s door and keeping them in remission for years.
But the truth is that
this happens for only a minority of patients. Now, doctors say, there is a new
imperative to develop a test that will identify in advance which patients will
benefit, sparing others the cost and possible side effects.
The drugs currently cost
about $150,000 a year per patient — even more for higher doses used in some
cases — and the health system is eventually expected to spend billions or even
tens of billions of dollars on the drugs each year.
“We don’t want to give
these to 100 percent of the patients if only 59 percent or 20 percent will
benefit,” said Dr. David R. Gandara, a professor and lung cancer specialist at
the University of California, Davis. Being able to test for a biomarker that
could predict the drugs’ efficacy “would make this new class of drugs easier on
the wallet, the national health wallet,” he said.
But developing such a
test has proved tricky so far, for ethical as well as scientific reasons. Some
doctors said it would be unfair to withhold the new drugs from patients based
on a test if there was still even a slight chance that the drugs would help.
“We don’t want to be
wrong, because these medicines have an effect that, in some cases, is durable
for years,” said Dr. Jedd D. Wolchok, chief of themelanoma and immunotherapeutics service
at the Memorial Sloan Kettering Cancer Center. “We don’t want to have an
imperfect biomarker.”
The need for such
biomarkers is illustrated in a study led by Dr. Wolchok that is to be presented
on Sunday in Chicago at the annual meeting of the American Society of Clinical
Oncology. The study is being published online by the New England Journal of
Medicine.
The 945-patient study
shows that the combination of two immune-boosting drugs from Bristol-Myers
Squibb — Opdivo and Yervoy — is more effective than either drug alone in
treating advanced melanoma. Patients treated with both drugs went a median of
11.5 months before their disease worsened, a longer reprieve than the 6.9 months
for those who received only Opdivo and 2.9 months for those who took Yervoy.
Dr. Antoni Ribas, a
melanoma specialist at the University of California, Los Angeles, who was not
involved in the study, said Opdivo alone might be just as good as the
combination for many patients, with far fewer side effects, but that a
biomarker test was needed.
“The combination is
outstanding, but we have to figure out who needs the combination as opposed to
the single agent,” he said.
The main test being
explored is for PD-L1, a protein produced by cancer cells that, in effect,
orders the immune system to stand down and not attack.
The Merck drug Keytruda,
Opdivo and other similar treatments work by keeping this “stand down” order
from being received by the immune cells. So it makes sense that the drugs work
best against tumors that are issuing such an order and that they may not work
at all against tumors that are not issuing the order.
Studies by Bristol-Myers
and Merck as well as Roche, which is also developing such a drug, have shown
that there was a much greater success rate using the drugs to treat tumors that
were positive for PD-L1.
Still, at least a small
number of patients whose tumors do not produce meaningful amounts of PD-L1 also
seem to benefit from these drugs. So some doctors say it is wrong to withhold
the drugs from patients whose tumors test negative for PD-L1.
In the melanoma study,
patients whose tumors were positive for PD-L1 did as well on Opdivo alone as
with the combination, as measured by the delay before their cancer worsened.
One implication might be that those patients should get only Opdivo, while
others should get the combination.
But Dr. Michael B.
Atkins, deputy director of the Georgetown Lombardi Comprehensive Cancer Center
in Washington, said that even for PD-L1-positive tumors, the combination was
better at shrinking the abnormalities.
“The biomarker isn’t good
enough to make any decisions on it,” said Dr. Atkins, who was not involved in
the study.
PD-L1 is not the only
possible biomarker. Scientists are finding that the drugs work best against
tumors with lots of mutations. Researchers reported on Friday that a genetic
signature could identify a small subset of patients with colorectal and other
types of cancer who would be likely to benefit from Keytruda.
Dr. Ribas and colleagues
suggest examining tumor samples to
see if immune cells are present. The drugs appear to work best when immune
cells are already in or near the tumor, ready to attack when the “stand down”
order is lifted by a drug. If the immune cells are not present, then merely
lifting the order may not be enough.
Merck is working with a
diagnostic company, NanoString Technologies, to develop a test that measures
activity levels in genes associated withimmune response.
A downside for drug
companies is that a test can narrow the market for a drug.
Shares of Bristol-Myers
fell nearly 7 percent on Friday based on what would seem to be positive
clinical trial results showing that Opdivo could prolong the lives of patients
with the most common form of lung cancer.
But there was a big
survival difference in patients with PD-L1-positive tumors and patients whose
tumors test negative for the protein. For those with PD-L1-negative tumors,
there was no real difference between Opdivo and the generic chemotherapy drug docetaxel. This
information dashed investors’ hopes that Opdivo might be used by all patients
with that form of lung cancer.
Opdivo did cause fewer
side effects than docetaxel, but insurers might not be willing to pay so much
more for that reason alone.
Docetaxel costs $6,000
for six cycles of treatment; Opdivo used for the same length of time costs
about $60,000, said Dr. Patrick W. Cobb, an oncologist in Billings, Mont.
“The cost of treating
these patients will be far higher than in the past,” Dr. Cobb said on a webinar
sponsored by Kantar Health, a consulting firm. “We really need a way of
determining which patients are likely to benefit from these agents.”
