U.S. Food and Drug Administration (FDA) has approved the expansion of the
indications of the anti-cancer drug olaparib.
- The US FDA has endorsed
olaparib suitable to treat certain breast cancers that have spread to
other parts of the body and have a specific inherited gene mutation
- Olaparib is currently
used to treat advanced ovarian cancers due to an inherited BRCA gene
- In a recent clinical trial in BRCA positive
metastatic breast cancer, olaparib provided a
more safe and effective treatment option than standard chemotherapy.
now be used to treat patients with certain breast cancers that have spread and
where the tumors are caused by a specifically inherited genetic mutation called
Olaparib is the first drug in its class, a PARP
protein inhibitor, to
be approved to treat breast cancer and specifically for such an indication.
Olaparib has been specifically indicated
for abnormal inherited (germline) breast cancer susceptibility (BRCA) gene, human epidermal growth factor
receptor 2 (HER2)-negative breast cancer that has spread to other parts of the
‘Olaparib has shown promise as an anti-cancer therapy in patients with HER-2 negative metastatic breast cancer and a germline BRCA mutation.’
These patients should have received
anti-cancer or chemotherapy
, either before or after cancer has spread. If the patients have
hormone receptor (HR)-positive breast cancer then they should
have either been treated with a prior hormonal (endocrine) therapy or be
considered inappropriate for endocrine treatment.
Patients have to undergo an FDA-approved
genetic test called the BRACAnalysis CDx to be eligible for treatment with
olaparib. To suit the current new indication, the FDA has also expanded the
approval of the BRACAnalysis CDx to include detection of BRCA mutations in
blood samples from patients with breast cancer.
The approval follows the positive results of
the Phase 3 OlympiAD Clinical Trial that evaluated the efficacy and safety of
Patients (302 in number) with HER2-negative
metastatic breast cancer with an inherited BRCA mutation and who had received
one or two previous chemotherapy regimens were eligible for the clinical trial.
They were randomly assigned (in a ratio of 2:1) to receive olaparib tablets
(300 mg twice daily) or standard therapy (capecitabine
vinorelbine in 21-day cycles).
The primary endpoint of the study was progression-free
survival or PFS
which is the length of time
after the treatment that the tumors do not grow significantly or do not get
of the Study
- The median
PFS was significantly longer (7 months in the olaparib
group) compared to 4.2 months for patients in the standard-therapy group.
- Patients in
the olaparib group had a better response rate (59.9%) compared with 28.8%
in the standard-therapy group.
- Olaparib also
proved to be a safer treatment option (the rates of grade 3 or higher
adverse events was 36.6% with olaparib, compared with 50.5% standard
therapy drugs). In addition, lesser patients had to discontinue due to the
toxic effects olaparib during the trial.
- Based on this
study, it appears that olaparib provides a safer and more effective
treatment option than standard chemotherapy for patients with
HER2-negative metastatic breast cancer and an inherited BRCA mutation.
Additional studies are also being done - assessing olaparib
as maintenance therapy after platinum-based treatment of breast cancer, and
studying PARP inhibitors in combination with immune checkpoint
In the US, olaparib is
already in the market
for the treatment of women who have advanced
ovarian cancer due to a
certain type of mutated inherited BRCA gene
and who have also received three or more
prior lines of chemotherapy.
Other indications for which olaparib is prescribed are epithelial
ovarian, fallopian tube or primary peritoneal cancers that have recurred.
"This class of drugs has been used to treat
advanced, BRCA-mutated ovarian cancer and has now shown efficacy in treating
certain types of BRCA-mutated breast cancer," said Richard Pazdur, M.D.,
director of the FDA's Oncology Center of Excellence and acting director of the
Office of Hematology and Oncology Products in the FDA's Center for Drug
Evaluation and Research. "This approval demonstrates the current paradigm of
developing drugs that target the underlying genetic causes of a cancer, often
across cancer types."
PARP and BRCA
DNA or deoxyribose nucleic acid contains the
genetic instructions used by most living organisms to grow, develop, function
and reproduce. It is thus a vital substance found in all the cells of the
body. By nature, one strand or both strands of DNA can break or get damaged and
when that happens, the DNA undergoes a repair mechanism.
Both PARP and BRCA are proteins that are involved in
repairing damaged DNA.
PARP or poly (ADP-ribose) polymerase proteins are enzymes that repair DNA when one
BRCA proteins repair DNA when both strands break.
Thus, BRCA genes normally work to prevent tumor development. When BRCA genes
get mutated (mutated-BRCA), the respective proteins function abnormally and
errors occur in the DNA repair. This may lead to certain cancers, including
Olaparib, being a PARP inhibitor, works by inhibiting
the activity of PARP enzymes, in other words, stalls the repair of damaged DNA.
With the BRCA genes
already mutated in cancerous cells, blocking PARP enzyme further prevents DNA
repair, resulting in a buildup of damaged DNA, leading to
cell death and possibly a slow-down or stoppage of tumor growth.
is cancer that starts in the breast
tissue. It is the most common form of cancer in women, affecting 1 in 8 women.
It can affect men too. BRCA1 and BRCA2 genes are two different genes (BRCA
is BReast CAncer gene) which when mutated can increase the risk of female
breast and ovarian cancers
. Around 20-25 percent of patients with
hereditary breast cancers have a BRCA mutation in their genes.
- FDA approves first treatment for breast cancer with a certain inherited genetic mutation - (https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm592347.htm)
- Mark Robson, M.D., Seock-Ah Im, M.D., Ph.D., El bieta Senkus, M.D., Ph.D., Binghe Xu, M.D., Ph.D., Susan M. Domchek, M.D., Norikazu Masuda, M.D., Ph.D., Suzette Delaloge, M.D., Wei Li, M.D., Nadine Tung, M.D., Anne Armstrong, M.D., Ph.D., Wenting Wu, Ph.D., Carsten Goessl, M.D., Sarah Runswick, Ph.D., and Pierfranco Conte, M.D. Olaparib for Metastatic Breast Cancer in Patients with a Germline BRCA Mutation. N Engl J Med 2017; 377:523-533August 10, 2017 DOI: 10.1056/NEJMoa1706450