Jimmy Carter announced that his brain
tumor had completely disappeared. He
had been treated with a Merck immunotherapy drug called pembrolizumab, marketed under the trade name Keytruda.
But the Food and Drug Administration
has only approved Keytruda and drugs
like it for melanoma, non-small cell lung
cancer and a few other conditions. For a
breast-cancer patient like D’Agostino, the
only option is to enroll in a clinical trial.
That’s what brought us to the Rutgers
Cancer Institute—to find out more about
the institute’s phase II clinical trial, a test
of Keytruda on patients with metastatic
triple negative breast cancer.
Six weeks later, D’Agostino would
join that trial. Her new tumor had
tested positive for a molecule called
PD-L1, which meant she was a fit for
the trial. But first, she had to navigate
a complicated medical maze that included 14 more doctor appointments,
two brain MRIs, five CAT scans, two
bone scans, a PET scan, two chest
x-rays and two biopsies—the second
of which was required because the lab
had lost tissue collected the first time.
Chemotherapy, the standard-bearer of
cancer treatment for the past 50 years,
was a medical accident that grew out of
the use of chemical warfare. Two pharmacologists hired by the U.S. government
at the beginning of World War II to find
an antidote to mustard gas had begun to
suspect that it might have properties that
could slow the growth of certain cancers.
A year into their research, when German
bombs struck a U. S. battleship secretly
carrying mustard gas, their hunch was
validated. Autopsies of victims of the
attack showed that the mustard gas had
profoundly suppressed their lymphatic
systems. By 1946, it was reported that nitrogen mustard injected into lymphoma
patients had indeed shrunk their tumors.
But immunotherapy—the newest
weapon in the war on cancer—was no
accident. It was a direct result of the
sequencing of the human genome, which
allowed scientists to begin discovering
the genetic mutations that cause cancer.
“All of a sudden, we could start to design
drugs that could be targeted against
a specific defect,” says Dr. Andre Goy
(pronounced gwah), director of the John
Theurer Cancer Center at Hackensack
University Medical Center.
The first breakthrough drug in this category was Gleevec, developed by scientists
at Ciba-Geigy in the late 1990s. Gleevec
turned chronic myeloid leukemia from a
death sentence into a chronic disease.
Oncologists and pharmaceutical companies are hoping that immunotherapy
drugs called PD- 1 checkpoint inhibitors—like the one Carter received—will
perform this miracle for other cancers.
Dr. Kim Hirshfield, director of the
precision medicine translational labora-
tory at the Rutgers Cancer Institute, and
D’Agostino’s primary oncologist, was
able to simplify the complex science
during our first visit. She pulled out a
pen and a piece of paper and started
drawing some squiggles. PD- 1 interacts
with PD-L1 or PD-L2, she explained,
tapping one of her squiggles. “That
puts an invisibility cloak over a tumor.”
Behind this cloak, a cancer can slip past
the patient’s immune system unde-
tected. A PD- 1 inhibitor—or immune
checkpoint inhibitor, it is commonly
called—removes the cloak and allows
the patient’s immune system to recog-
nize the tumor and destroy it.
An added bonus: while immunotherapy drugs are administered the same
way as most chemotherapy—by intravenous infusion—they generally don’t
cause the dreaded hair loss and nausea.
What’s more, when they do bring a pa-
tient into remission, it can last for years.
Early successes have led to something
of a pharmaceutical arms race. According to The Cancer Letter, a publication
that covers cancer research, there are
more than 800 ongoing clinical trials
involving checkpoint inhibitors.
As it turns out, the two companies
that have the strongest positions in
this market—Merck and Bristol-Myers
Squibb—happen to be in New Jersey.
Merck is headquartered in Kenilworth.
Squibb, though based in New York, has
6,600 employees in the Princeton area,
including many of its R&D employees.
“Squibb and Merck are kind of duking
it out,” says Ed Silverman, Pharmalot
columnist and senior writer at Stat.
“Cancer is the big kahuna—a big, myste-
rious, evil disease that has been vexing
everyone so long that anything that
might make a dent is a big deal.”
“All of a sudden, we could start to design drugs that
Dr. Kim Hirshfield, head of specialized medicine
at Rutgers Cancer
Institute of New
Jersey in New
with her loving
bedside manner. “I feel very
her hands,” says