OLAPARIB OVARIAN CANCER TREATMENTS
A promising new treatment option for ovarian cancer patients made news this week when the FDA approved a New Drug Application (NDA) for olaparib (Lynparza) tablets, “for use in platinum-sensitive, relapsed ovarian cancers in the maintenance setting” – that is, for people with advanced cancer who have already completed an initial regimen of surgery and chemotherapy, and who have responded positively to platinum-based cancer treatment agents (Oncology Times/FDA). Olaparib ovarian cancer therapies produced some exciting results in clinical trials, delaying tumor growth and increasing survival rates in women fighting an advanced disease.
But how exactly does olaparib ovarian cancer therapies work? And – if you’re battling ovarian cancer – how do you know if olaparib ovarian cancer therapies might be a good option for you? Navigating the landscape of new drug therapies can be overwhelming, so let’s break it down from the beginning.
OVARIAN CANCER BASICS
Ovarian cancer is the second-most common reproductive cancer in American women following endometrial (or uterine) cancer, but it is also the deadliest as it is exceedingly difficult to detect early. Caucasian women, women who have never given birth, post-menopausal women, and women with a family history of breast, ovarian, or uterine cancer tend to be at greater risk of developing ovarian cancer. According to the American Cancer Society, ovarian cancer is rare in women under the age of 40 and half of all ovarian cancers are diagnosed in patients over 63 (ACA).
Certain inherited traits, such as a mutation in the BRCA1 and BRCA2 genes, may also put a woman at increased risk of developing breast and ovarian cancers (you may have heard of the BRCA-mutation by way of Angelina Jolie, who underwent a preventative double mastectomy in 2013 after losing her mother to ovarian cancer and learning she carried an abnormal copy of the gene). When functioning normally in most people, these genes tell cells “to make a protein that helps repair damage to DNA. So people who inherit a faulty copy are less able to repair damage that accumulates in their DNA over time. And so they’re at higher risk of cancer” (Cancer Research UK).
Doctors will typically recommend surgery followed by a course of chemotherapy for most ovarian cancer patients. The specific type of chemotherapy you will receive should be determined by your oncologist after diagnosis and staging, as there are are a number of chemotherapy drugs in wide use today and the most appropriate course varies from woman to woman. The most common agents for treating ovarian cancer are taxanes (paclitaxel or docetaxel) and platinum agents (carboplatin or cisplatin), as “studies have demonstrated that platinum- and taxane-containing chemotherapy improves the survival of women with ovarian cancer over other types of regimens” (UpToDate).
So how does olaparib ovarian cancer therapies fit into this traditional treatment plan?
PARP INHIBITORS AS A MAINTENANCE THERAPY
Olaparib (Lynparza) is part of a class of pharmaceuticals called PARP inhibitors. PARPs – or, Poly (ADP-ribose) polymerases – are enzymes that help repair damaged DNA. As a targeted cancer therapy against malignant cells, PARP inhibitors “may help keep cancer cells from repairing their [own] damaged DNA, causing them to die.” (NIH/National Cancer Institute).
Recent studies have shown that PARP inhibitors hold significant promise as a maintenance therapy, particularly by increasing progression-free survival (PFS) rates in those patients with BRCA-mutated cancers. Olaparib ovarian cancer therapies itself has been around since 2014, when the FDA approved the drug in a 400mg capsule formulation for use in patients with BRCA-mutated advanced ovarian cancers (Oncology Times/FDA). More recently, olaparib’s phase II and III trials suggested that even patients without BRCA cancers may see positive results from treatment with the drug, even though people with the mutation still saw the greatest benefit (MedPage Today). And Olaparib ovarian cancer therapies is not the only PARP inhibitor in the game, or to make headlines in recent weeks: niraparib (Zejula) was approved by the FDA on March 27 to treat recurrent epithelial ovarian, fallopian tube, and primary peritoneal cancers regardless of the patient’s genetic status (FDA).
To be clear, PARP inhibitors like olaparib and niraparib do not replace a conventional strategy of surgery and chemotherapy, but rather expand the arsenal of options available to doctors and their patients during the following maintenance phase of treatment. It’s important to remember that there is no set standard or single solution for maintenance therapy: some doctors, for example, may advocate simple clinical observation. Other methods (such as maintenance chemotherapy) remain under consideration and research, and new information continues to emerge by the day. However, maintenance chemotherapy performed rather poorly in another recent study, having a negligible effect on overall survival rates and possibly even encouraging chemoresistance in some people (Medpage Today). For patients who wish to avoid additional lines of chemotherapy (along with its associated toxicity), the trend towards PARP inhibitors may come as somewhat encouraging news.
PARP inhibitors, however, are not side-effect free: anemia, nausea, and abdominal pain are just some of the adverse effects associated with both olaparib and niraparib, though some of these symptoms were also common in control groups taking placebo. And for some people, PARP inhibitors may come with some “serious risks”: the FDA notes that niraparib may cause “hypertension, severe increase in blood pressure (hypertensive crisis), bone marrow problems (myelodysplastic syndrome), a type of cancer of the blood called acute myeloid leukemia and low levels of blood cells in the bone marrow (bone marrow suppression)” (FDA). As with any course of therapy, only you and your doctor can determine if the potential benefits of trying a PARP inhibitor outweigh the risks.
CONCLUSION
So, what’s the bottom line? PARP inhibitors may be an exciting prospect for more people than we previously believed, not just those with BRCA-mutated cancers. If PARP inhibitors are news to you, or if you previously thought you couldn’t benefit from one because of your BRCA status, you may wish to to talk to your doctor as your options may have changed with the emergence and approval of these new drug therapies. And for women who do have BRCA-related ovarian cancer, the expanded acceptance of PARP inhibitors is excellent news indeed.
As with any new therapy, we continue to learn new things about PARP inhibitors every day. So keep reading. Don’t be afraid to ask questions. And always remember: it’s up to you to work with your doctor to choose the specific treatment strategy that’s best for you.
Suffering from ovarian cancer? Contact Oncologic Advisors for a second opinion and navigational advice.
REFERENCES
Oncology Times, FDA Actions & Updates – New Drug Action Approved for Olaparib in Ovarian Cancer Use. March 28, 2017.
American Cancer Society (ACA) – About Ovarian Cancer.
https://www.cancer.org/cancer/ovarian-cancer/about.html
Cancer Research UK – Angelina Jolie, inherited breast cancer and the BRCA1 gene. Henry Scowcroft, May 14, 2013.
UpToDate – Patient Education: First-line medical treatment of epithelial ovarian cancer (Beyond the Basics). Thomas J. Herzog, MD, Vincent E. Herrin MD, last updated February 9, 2017.
https://www.uptodate.com/contents/first-line-medical-treatment-of-epithelial-ovarian-cancer-beyond-the-basics?source=search_result&search=%E2%80%9Cstudies%20have%20demonstrated%20that%20platinum-%20and%20taxane-containing%20chemotherapy%20improves%20the%20survival%20of%20women%20with%20ovarian%20cancer%20over%20other%20types%20of%20regimens%E2%80%9D&selectedTitle=1~1
NIH/National Cancer Institute – NCI Dictionary of Cancer Terms.
https://www.cancer.gov/publications/dictionaries/cancer-terms?cdrid=660869
MedPage Today – PARP Inhibitor Extends PFS in Ovarian Cancer. Charles Bankhead, March 15, 2017.
https://www.medpagetoday.com/meetingcoverage/sgo/63854
FDA News Release – FDA approves maintenance treatment for recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancers. March 27, 2017.
