A drug that targets faulty gene repair may buy more time for some men with advanced prostate cancer, a new clinical trial finds.
Experts called the study “landmark,” because it zeroed in on men with particular gene mutations that can be targeted with newer drug therapies.
It’s an approach that is already used in treating breast, ovarian and lung cancers.
Specifically, the trial tested a drug called Lynparza (olaparib), which is currently approved to treat certain patients with breast or ovarian cancers linked to mutations in the BRCA genes.
When BRCA is working properly, it helps repair damaged DNA in body cells that can lead to cancer. When the gene is altered, those repair mechanisms go awry.
BRCA mutations do not only lead to breast and ovarian cancers, though. They also help drive some cases of prostate cancer.
In the new trial, researchers recruited men with advanced prostate cancer who had alterations in BRCA or certain other genes involved in DNA repair.
The investigators found that, compared with standard hormonal therapy, Lynparza delayed patients’ cancer progression for a median of about three months. That means half the patients saw a longer delay and half a shorter one.
Along with that delay, the drug slowed down patients’ pain progression.
“Delaying the cancer from growing is meaningful,” said Dr. Maha Hussain, who led the trial, which was funded by drug makers Astra Zeneca and Merck.
“At the end of the day, patients want to live longer—and also better,” added Hussain, a professor at Northwestern University Feinberg School of Medicine, in Chicago.
She was to present the findings at the annual meeting of the European Society for Medical Oncology, in Barcelona. Studies reported at meetings are generally considered preliminary until they are published in a peer-reviewed journal.
Lynparza is one of a newer class of drugs called PARP inhibitors, which block a protein that cancer cells need to keep their DNA healthy. Without it, those cells may die. Cancer cells with defects in DNA-repair genes are especially vulnerable to PARP inhibitors.
The drug class is part of a wider trend in cancer treatment, toward “targeted therapies”—where medications are tailored to target certain molecules in cancer cells that help them grow and spread.
A range of targeted drugs are available for common cancers, such as breast and lung, but prostate cancer has “lagged behind,” Hussain said.
Dr. Eleni Efstathiou, of MD Anderson Cancer Center in Houston, described the new trial as landmark.
“Overall, these data show that, like breast and lung cancers, prostate cancer is not one but many different diseases,” Efstathiou said. “We need to start identifying different groups of patients and treating them with targeted therapy.”
She noted that only a fairly small percentage of prostate cancer patients would have alterations in DNA-repair genes—which can be inherited or arise as the cancer progresses.
And doctors do not routinely screen cancers for all those gene flaws.
Screening for inherited mutations is “becoming part of guidelines,” Efstathiou noted, but screening for non-inherited alternations is not yet done.
For the latest trial, the researchers screened 4,425 men with advanced prostate cancer that had spread to distant sites in the body and was not responding to standard hormonal therapy.
The investigators ended up with 245 patients with alterations in either BRCA or another gene called ATM. A second group of 142 patients had alterations in any of 12 other genes tied to flawed DNA repair.
Patients in both groups were randomly assigned to either take Lynparza tablets or start one of two newer hormonal therapies.
Overall, Lynparza patients saw their cancer advance more slowly, with the difference being clearer in the group with BRCA or ATM defects.
For those men, cancer progression was delayed by a median of 7.4 months, versus 3.5 months among patients on hormonal therapy. A preliminary analysis suggested their overall survival was also better—a median of 18.5 months, versus 15 months.
Lynparza does have side effects, including anemia and nausea, Efstathiou pointed out, which can make it difficult to stick with the drug. Just over 16% of Lynparza patients in the trial stopped treatment due to side effects.
The drug is not yet approved for prostate cancer, though some doctors use it “off-label” for certain patients, Hussain noted.
At this point, Efstathiou said, doctors may want to screen for DNA-repair mutations in the tumors of men with advanced prostate cancer, since “we now have evidence it can be successfully targeted.”
Like other targeted drugs, Lynparza carries a hefty price tag: Researchers have estimated that it costs more than $234,000 to extend a patient’s life by one year.
Reprinted with permission from Spectrum Health Beat.
