PARP Inhibitors Before Surgery for Ovarian Cancer
- PARP inhibitors are a class of drugs that treat ovarian cancer at the genetic level.
- New research shows that ovarian cancers patients may benefit from PARP inhibitors before surgery.
- It’s important to know that it’s a preliminary study and does not yet support the use of one particular PARP inhibitor, olaparib (brand name Lynparza), in the neoadjuvant setting.
- Still, the findings could provide a potential template for how doctors might vet targeted therapies earlier in the treatment continuum.
The study was presented at the 2023 Annual Meeting on Women’s Cancer from the Society of Gynecologic Oncology (SGO). Once a year, thousands of gynecologic oncologists, surgeons and medical oncologists from around the world come together to learn and discuss the latest advancements in the fight against ovarian cancer.Read More
How PARP Inhibitors Work
One of the key things to know about PARP inhibitors is that your genetic makeup and specific features of your cancer will have a significant impact on how effective these drugs may be. Experts tell SurvivorNet that every woman with ovarian cancer should get a genetic test to determine if they have a mutation called BRCA, because the mutation enables PARP inhibitors to function much more powerfully. Importantly, there is increasing data that even women without BRCA mutations can still derive some benefit from these drugs.
PARP inhibitors interrupt the process of single-stranded DNA repair, an essential part of cell replication. Defects in DNA repair ultimately cause cell death. PARP inhibitors work best when there is a second error in DNA repair, such as that caused by a mutation in BRCA. BRCA is a critical player in homologous recombination, a highly effective double-stranded DNA repair process. BRCA is not the only important part of homologous recombination, other genes are involved. The label homologous recombination deficient (HRD) indicates a tumor which has one of many possible errors in the double stranded DNA repair process of homologous recombination.
WATCH: Genetic Testing & Ovarian Cancer
Promising Findings on PARP Inhibitors
Administering PARP inhibitor olaparib (brand name Lynparza) prior to surgical intervention and chemotherapy in ovarian cancer patients – a new approach – is feasible and resulted in favorable surgical options, managable adverse events, and positive health outcomes, according to results from the Neoadjuvant Olaparib Window (NOW) Trial presented by Dr. Shannon N. Westin and collegues at the SGO’s 2023 Annual Meeting on Women’s Cancer. However, the study focused only on 15 patients with germline mutations. Germline mutations are changes to your DNA that you inherit from the egg and sperm cells during conception.
Results from this study showed that olaparib given in the neoadjuvant setting was feasible, with 100% of trial participants able to receive the planned two cycles. Of 93% participants able to undergo subsequent surgery, all achieved optimal tumor reduction.
Among patients treated first with two cycles of neoadjuvant olaparib, followed by surgery and adjuvant chemotherapy, 85% had no evidence of disease at the completion of all therapies.
Side effects during olaparib treatment were as expected, with abdominal pain, constipation, anemia, nausea, and pain observed most commonly. The only severe adverse event reported was grade 3 (severe but not immediately life-threatening) anemia in three patients. Anemia is a condition in which the body does not have enough healthy red blood cells.
It’s important to note that this was a feasilibility study performed on only 15 patients. Feasibility studies are used to determine whether an intervention is appropriate for further testing; in other words, they enable researchers to assess whether or not the ideas and findings can be shaped to be relevant and sustainable.
About the Neoadjuvant Olaparib Window (NOW) Trial
SurvivorNet also spoke with Dr. Ritu Salani, director of the Gynecologic Oncology Division at UCLA Health. She said the study “presents a novel approach to BRCA mutation (RAD51C and PALB2 mutation) carriers. It is very provocative and has the potential to be practice changing but will need to have a streamlined process for genetic testing to identify the patients in who this treatment strategy is most effective for in a timely fashion and more data to determine the exact treatment regimen before and after surgery.”
The NOW Trial (NCT03943173) was a single arm, open label pilot study for advanced stage, high grade epithelial ovarian, peritoneal, or fallopian tube carcinoma. All patients had germline mutation in BRCA1, BRCA2, RAD51C or PALB2. Fifteen total patients were treated, with median age of 56 years. Forty percent had advanced (stage four) disease.
Historically, PARP usage has followed cytotoxic chemotherapy as a maintenance medication, often taken long-term amongst patients with ovarian cancer.
These new findings help justify further research studies to determine if PARP can be given in lieu of chemotherapy in the neoadjuvant setting – a new usage of the medication.
WATCH: Who Can Receive PARP Inhibitors?
Side Effects Of PARP Inhibitors
Unfortunately, like all cancer therapies, PARP inhibitors come with side effects. Whether or not you’ll experience significant side effects from PARP inhibitors depends on several factors, including which PARP inhibitor you’re taking, what dose you are ingesting, and whether you’re using it alone or in combination with other therapies.
Still, the side effects of most PARP inhibitor protocols include:
- Nausea or vomiting
- Upset stomach
These side effects can be intolerable for some patients, but in almost every case, doctors can offer options to alleviate or even eliminate them.
Since PARP inhibitors disrupt how cells repair damaged DNA, killing off tumor cells and healthy cells simultaneously, the bone marrow and blood cells may take a hit. As a result, a subset of patients encounter side effects of PARP inhibitor treatment related to bone marrow suppression such as reduced blood cell and platelet counts.
- Anemia (a drop in the red blood cells), which may result in fatigue
- Thrombocytopenia (a drop in the platelet count), which can cause easy bruising and excessive bleeding
- Neutropenia (a drop in the white blood cell count), which can leave people more susceptible to infection
“[Patients] would always feel like they’re fatigued. We would have to watch their labs. [They would have] more [office] visits, and more assessments with imaging.” However, for the appropriate patients, “[PARPs] can be a good choice that [are] worth the side effects,” Dr. Whitfield Growdon, gynecologist-oncologist at New York University Langone’s Perlmutter Cancer Center, told SurvivorNet in a previous conversation.
Education and transparent provider-patient discussions about PARP-inhibitor eligibility, as well as the side effects and high prices associated with these drugs, can make a dramatic difference in treatment results.
About The Society of Gynecologic Oncology
The Society of Gynecologic Oncology (SGO) is the premier medical specialty society for health care professionals trained in the comprehensive management of gynecologic cancers. As a 501(c)(6) organization, SGO contributes to the advancement of gyn cancer care by encouraging research, providing education, raising standards of practice, advocating for patients and members and collaborating with other domestic and international organizations.
Questions to Ask Your Doctor
If you ovarian cancer – or are wondering about your risk – and have questions about whether PARP inhibitors are a viable treatment option for you, here are some ways you can discuss it with your doctor:
- Should I be tested for BRCA mutation?
- Am I eligible to receive Lynparza before surgery?
- How will I feel during treatment?
- What are the most common side effects of Lynparza?
- What will my treatment cost? Will my treatment be covered by my medical insurance company?
- Should I get a second option regarding my diagnosis?
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