Cancer treatments rely on biopsies—the removal of cells or tissue
for examination by a pathologist—for definitive diagnosis. Biopsies
are invasive, sometimes to the point of requiring surgery. A new type
of biopsy, under investigation at Torrance Memorial Physician Network–Cancer
Care (a medical group affiliated with the Hunt Cancer Institute at Torrance
Memorial Medical Center), is paving the way to become a much less invasive
method to detect and treat cancer.
Known as liquid biopsies, these are blood tests that analyze pieces of
tumor DNA or other genetic material “shed” from tumor cells
circulating in the blood. Oncologists with Torrance Memorial Physician
Network–Cancer Care are partnering with liquid biopsy companies
to develop these new blood tests that can detect cancer and also help
direct treatment.
One of these research clinical trials is a national multicenter feasibility
trial in partnership with a company called Genomic Health.
“We are the leading research group for Genomic Health in developing
a DNA/RNA blood test to diagnose breast cancer at a very early stage in
its development,” says David Chan, MD, medical oncologist with Physician
Network–Cancer Care and the program director for oncology with the
Torrance Memorial Hunt Cancer Institute. “If successful, this test
would also be helpful in monitoring the progress of breast cancer patients.”
So far 370 breast cancer patients have donated their time and blood specimens
over the past two years for this trial’s data points. The promise
of the trial is great—it gives doctors the ability to have an extremely
accurate blood test to monitor disease status in a breast cancer patient.
A similar trial underway in the oncology program is working with another
biotech company, Natera, to develop a liquid biopsy for the early detection
of lung cancer in patients with lung nodules. Dr. Chan notes that in their
diagnostic center they find around 500 lung nodules on computerized tomography
(CT) scans every year. The nodules may be from previous lung infections
or scarring and not necessarily cancer, but patients generally need repeat
scans and sometimes biopsies to determine the cause. Currently lung nodule
patients are donating blood specimens to help in the development of a
DNA/RNA test to diagnose whether the nodules are due to cancer or are
benign. If effective, this could prevent the need for multiple scans and
invasive biopsies to detect a malignancy.
TARGETED GENE TREATMENT
Detection is just one of the hopes for liquid biopsies. Another is identifying
specific genetic markers or mutations that can help physicians choose
the most appropriate course of care.
“When an oncologist can find an actionable mutation (i.e., a mutation
for which there is an available targeted therapy), this can open up brand
new treatment options for patients,” says Andrew Horodner, MD, medical
oncologist with Torrance Memorial Physician Network–Cancer Care
and chairman of the tumor board and vice chair of the oncology committee
with the Torrance Memorial Hunt Cancer Institute. Typically an oncologist
employs chemotherapy against cancer. While often effective, the therapies
can be toxic, notes Dr. Horodner. Chemotherapy acts on all actively dividing
cells, so it can adversely affect multiple organs.
In contrast, “Therapies that hit a specific target in the cancer
cell are more focused and generally better tolerated due to fewer side
effects,” says Dr. Horodner. “Many targeted therapies are
already approved to treat malignancies. But we are really still just at
the beginning in terms of learning which specific mutations drive certain
cancers to develop. These driver mutations may be different in one patient
versus another.”
By using liquid biopsies to identify and target specific mutations, physicians
can offer more individualized cancer care. For instance, one of the clinical
trials open at Torrance Memorial Physician Network–Cancer Care focuses
on patients who have run out of standard treatment options for their cancer.
When this is the case, they can have a liquid biopsy. If they find a specific
mutation in a gene, such as BRAF, EGFR or sonic hedgehog (yes, the actual
name of a gene), then the patient can qualify for a drug that targets
the protein produced by these mutant genes, Dr. Horodner explains. By
enrolling in the clinical trial, the patients are provided the drug by
the sponsoring company, Science 37, at no cost to them or their insurance
companies.
Research has also found that mutations can develop while a patient is on
anti-cancer therapy, leading to resistance and tumor growth. While a traditional
tumor biopsy provides a static snapshot of the genetic profile of a cancer,
a liquid biopsy can help provide a picture of how a tumor changes over
time. “It’s becoming clear that treatment can result in new
changes in the cancer that alter the DNA profile. That may open new opportunities
to treat with a second targeted drug,” says Dr. Chan.
ADDED BENEFITS FOR PATIENTS
Because there are so many clinical trials at Torrance Memorial Physician
Network–Cancer Care, many patients can be involved in more than
one clinical trial over the course of their treatment, which can be valuable
when an initial treatment isn’t effective. For instance, because
Torrance Memorial Physician Network–Cancer Care works with the research
network DAVA, the hospital can offer a trial for non-small cell lung cancer
patients for whom first line therapy has not worked. The study looks for
the Exon 14 skipping mutation. If found, patients can qualify for a therapy
aimed at this mutation.
Liquid biopsies for cancer diagnosis and monitoring are not yet standard
of care, and some of the treatments targeting specific mutations on these
trials do not yet have FDA approval. “At Torrance Memorial Physician
Network–Cancer Care, we are on the cutting edge in terms of using
these tests to guide treatment decisions and in terms of having clinical
trials available to our patients,” notes Dr. Horodner. “Our
patients can use the results of these tests to gain access to treatments
not readily available to the general public by enrolling in our clinical
trials. Oncologists from other clinics can refer patients to us if they
have exhausted treatment options and their patients have these targetable
mutations.”
Finding these new mutations, and having treatment available for them, has
directly benefited patients. For instance, a patient treated with Tarceva
for a type of lung cancer with a EGFR gene mutation was doing well for
awhile, but her cancer started to worsen. Dr. Horodner and colleagues
did a liquid biopsy and found the tumor developed a driver mutation called
T790M, for which the FDA has an approved drug named Tagrisso. “Our
patient was able to receive this drug and her disease is responding well.
She has minimal side effects."
THE FUTUTRE OF LIQUID BIOPSY
Although the promise of liquid biopsy is great, it wasn't until June
2016 that the FDA approved the first liquid biopsy for use in cancer.
Known as the Cobas EGFR Mutation Test v2, the test picks up certain mutations
in the epidermal growth factor receptor (EGFR) gene that makes patients
with advanced non-small cell lung cancer eligible for treatment with Tarceva
(erlotinib), which targets EGFR mutations. More approvals are likely on
the horizon, but first liquid biopsy testing must prove it can detect
alterations in genes consistent with what is detected by using traditional
tumor bioopsy methods. "With time and maturation of data and promising
results, these tests will likely become part of the standard oncology
diagnostic algorithm," says medical oncologist, Andrew Horodner, MD.