A drug used to treat breast
and ovarian cancers tied to certain genetic mutations may help combat some of
the most severe cases of prostate cancer.
Researchers tested the drug,
called olaparib, in a randomized clinical trial of nearly 400 men with advanced
prostate cancer and a mutation in one of several genes involved in repairing
damaged DNA, such as BRCA1 and BRCA2. These genetic defects raise the
risk of certain cancers, including breast and ovarian (SN: 4/7/15). Up to 30
percent of men with the hardest-to-treat prostate cancers also have mutations
in this type of gene.
In the Phase III clinical
trial, designed to compare the new treatment with current standard treatment, the
men were split into two groups based on their genetic mutations. The 245 men in
one group had mutations in some of the genes most commonly associated with
breast and ovarian cancer (BRCA1, BRCA2 and ATM), while the 142 men in the other group had other mutations in DNA-repair
genes. About two-thirds of men in each group took olaparib.
Overall in men given
olaparib, the disease progressed more slowly compared with those on standard
treatment drugs that deprive cancer cells of the male hormone testosterone. After
a year, about 22 percent of men taking olaparib had no signs that their cancer
was progressing, compared with 13.5 percent of men on the standard treatments, the
researchers reported September 30 in Barcelona at the European Society of Medical Oncology meeting.
The difference was greater
in the group with the BRCA1, BRCA2 and ATM mutations: 28 percent had no signs their cancer was progressing
compared with 9.4 percent receiving standard treatment. Alterations in the BRCA genes are often associated with
responding to drugs that work similarly to olaparib, says Maha Hussain, an oncologist
at Northwestern University Feinberg School of Medicine in Chicago who presented
the findings at the oncology meeting.
In patients with measurable
tumors within the BRCA group, tumor
sizes shrank in a third of those on olaparib, compared with 2.3 percent of those
on the standard therapy.
But while the new treatment
looks promising so far, potentially buying some patients a few more months, it’s
too early to say how the drug will impact overall survival. The clinical trial, cofunded by
pharmaceutical companies that manufacture olaparib, AstraZeneca and Merck &
Co, is slated to continue into early 2021.
Olaparib is a PARP inhibitor:
The drug blocks the PARP enzyme that repairs broken DNA. Cancer cells thrive in
a Goldilocks zone of DNA damage — just enough that the cells become carcinogenic, but
not so much that they die. Interfering with the PARP enzyme makes cells more
likely to go haywire and, eventually, commit cell suicide.
The drug works similarly in prostate
cancer as it does in ovarian and breast cancers. “Essentially, it’s going after
the same target: PARP,” Hussain says.
The U.S. Food and Drug
Administration has approved olaparib for breast and ovarian cancers, but not for prostate cancer. If the FDA one day approves
the drug’s use for severe cases of the disease, it will be one of the first
times that a precision medicine approach — or the idea of
personalizing a therapy based on a person’s genes — has been used to treat prostate
“[Prostate cancer therapy]
has been, generally, a one-size-fits-all approach,” Hussain says. “With regard
to precision medicine, I think that we’ve opened up the door.”
In the United States, 1 in 9
men will be diagnosed with prostate cancer in his lifetime, according to the
American Cancer Society. That makes the disease the second most common type of
cancer in American men, after skin cancer. It’s often treatable. Doctors can remove the prostate through surgery or destroy cancer
cells with radiation or chemotherapy. They may also use various drugs to decrease
male hormone levels or ramp up the body’s immune system to help fight the
But, for some patients,
these therapies don’t work. About 30,000 men in the United States die from prostate
cancer each year.
“My hope is that we’re going
to be doing more and more research to better personalize care for the
individual patient,” Hussain says.
For patients with BRCA or ATM mutations, the researchers also found that olaparib appeared to
delay pain from worsening. After a year, about 80 percent of men reported that
their pain had stayed the same, compared with just over 40 percent of those
receiving the other drugs.
Almost all of the men,
regardless if they took olaparib or standard hormonal drugs, reported side
effects like anemia, nausea or fatigue. However, those on olaparib had higher
rates of anemia and reported more severe side effects.
The findings indicate that,
for patients with these specific mutations, a PARP inhibitor like olaparib may
work better than trying another type of hormonal therapy, says William Dahut, an
oncologist and the scientific director for clinical research at the Center for
Cancer Research in Bethesda, Md.
However, testing prostate
cancer patients for genetic mutations isn’t routine unless the cancer begins
spreading throughout the body, he says. “I think this will lead to many more men
being tested to see if they have these genetic abnormalities.”
If men are tested for these
genetic mutations very early on, then doctors may be able to predict which
patients might benefit from starting a PARP-inhibitor drug sooner. “It’s at
least possible that by using these drugs earlier, they may even have a bigger
impact,” Dahut says.
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