Results from three major ovarian cancer studies just revealed that a relatively new class of drugs called PARP inhibitors are quickly becoming what’s called the “standard-of-care” — that is, the “go-to” treatment — for women who have just been diagnosed with ovarian cancer. The most exciting of the three studies, called “PRIMA,” showed that taking a specific PARP inhibitor drug called Zejula (also known as “niraparib”) after a response to platinum-based chemotherapy can extend the amount of time someone lives without their cancer getting worse by roughly five and a half months, which is actually a pretty significant amount of time.
“It is likely that this will become the new standard of care for all women newly diagnosed with ovarian cancers,” Dr. Douglas Levine, a gynecologic oncologist at NYU Langone Health, told SurvivorNet. Dr. Michael Birrer, a Professor at the University of Alabama Birmingham O’Neal Comprehensive Cancer Center, said the same, adding that the reason this study is so exciting is that all women with newly-diagnosed ovarian cancer were included in this five-month benefit, not just women whose cancers had BRCA mutations. Previously, it was thought that only women whose cancers had BRCA mutations could benefit from PARP inhibitors early on in their treatment.Read More
Another Benefit — PARP Inhibitors And Chemo At the Same Time
The second study, called VELIA, showed that taking another PARP inhibitor drug called veliparib along with chemotherapy, and then continuing to take it after chemo extended the amount of time someone could live without their cancer getting any worse by roughly six months.
“Veliparib added to chemotherapy and continued as maintenance significantly extended PFS [progression-free survival] in all patient cohorts with newly diagnosed high-grade serous ovarian carcinoma, regardless of biomarker, choice of surgery, or paclitaxel regimen,” Dr. Robert L. Coleman, a gynecologic oncologist, professor, and surgeon at the MD Anderson Cancer Center and the lead author of the VELIA study explained. “Veliparib in combination with chemotherapy should be considered a new treatment option for women with newly diagnosed, advanced-stage serous ovarian cancer.”
Avastin Plus Parp Inhibitors
Finally, a study called PAOLA showed that, after chemotherapy, women with newly-diagnosed ovarian cancer lived about six months longer without their cancers getting any worse by taking a drug called Avastin (bevacizumab) in combination with a PARP inhibitor drug called Lynparza (also called “olaparib”) compared with just taking the drug bevacizumab alone.
Doctors are considering all three of these ovarian cancer studies as game-changers in that they show that PARP inhibitors can be an effective treatment early-on for all women — not just women with specific genetic characteristics in their tumors.
The Greatest Benefit With BRCA Mutations or “HRD”
That being said, the studies did show that the genetic characteristics could make the drugs even more effective. For instance, in the PRIMA study, women who had something called “homologous recombination deficiency” in their tumors lived about twice as long without their cancers getting any worse when they took the PARP inhibitor Zejula right after chemo, compared with women who did not take Zejula. And women with BRCA mutations saw an even greater benefit in the VELIA study.
The reason that these two genetic characteristics (BRCA mutations and homologous recombination deficiency) increased the benefit of these PARP inhibitor drugs has to do with the way PARP inhibitors work.
PARP inhibitor drugs work by preventing cancer cells that have been damaged—often during the course of chemotherapy treatment—from naturally healing. To accomplish this, and, in turn, effectively kill the cancer cell, the PARP-inhibitor drug blocks the necessary mechanism of repair, the PARP enzyme, which the cancer cell requires to its broken DNA.
“The use of PARP inhibitors has really kind of exploded in ovarian cancer and it’s very exciting,” Dr. Ritu Salani, a gynecologic oncologist at Ohio State University Wexner Medical Center, told SurvivorNet in a previous conversation about PARP inhibitors.
Dr. Rebecca Arend of the University of Alabama-Birmingham Comprehensive Cancer Center spoke with SurvivorNet about homologous recombination deficiency and how it can play into ovarian cancer treatment.
When someone’s ovarian cancer cells have either a BRCA mutation or a genetic characteristic called “homologous recombination deficiency,” (“HRD”) that means that the cells already have a difficult time repairing themselves after damage (or at least, they have a more difficult time than cancers without HRD). Because the PARP inhibitors make the repair process even more difficult, cancers with HRD usually respond the best to PARP inhibitors. In the PRIMA study, people with HRD who took Zejula lived almost double the amount of time without their cancers getting any worse than people who didn’t take Zejula. That’s a major improvement.
Ultimately, the studies showed that everyone can reap the benefits of these drugs early on in the course of their treatment, but that women with BRCA mutations or “HRD” saw the greatest benefit.
Either which way, the study results are promising, and will no doubt change the way women with ovarian cancer are treated when they first receive a diagnosis.
Side Effects And Considerations With PARP Inhibitors
But as more studies like these continue to expand the group of women with ovarian cancer who can benefit from PARP inhibitors (and the experts say several other big studies are coming out soon), it’s important to pay attention to the side effects and other considerations that go along with these drugs.
“For some women, the toxicity [side effects] will outweigh the benefit,” Dr. Bobbie J. Rimel, an OB/GYN and oncologist at Cedars-Sinai Medical Center, told SurvivorNet, explaining that the fatigue that can come with PARP inhibitors is a serious and common side effect. In some cases, though, experts say the benefits of PARP inhibitors can outweigh the difficult fatigue.
“Despite the fact that some women have increased fatigue — partially, that’s because of the anemia that the drug causes — it is still worth that cost in the survival advantage that women are getting,” Dr. Rebecca Arend of the University of Alabama-Birmingham Comprehensive Cancer Center previously told SurvivorNet.
And in a previous conversation about PARP inhibitors, Dr. Emese Zsiros, a gynecologic oncologist at the Roswell Park Cancer Institute told SurvivorNet that a lot of women who take PARP inhibitors experience nausea, vomiting, constipation, or diarrhea. Doctors are getting better at helping women manage these side effects every day, but sometimes they can be severe, making it important to talk to your doctor about whether they outweigh the benefits of the drugs.
“We have to weigh the risk and benefit of prescribing these medications to our patients,” Dr. Zsirors said, adding that they aren’t cheap, either. “There is a significant financial toxicity when we prescribe these medications. I think there is a lot of cost-benefit ratio, and also there is a significant side effect.”