Update: New FDA approval of PARP inhibitor for maintenance therapy in ovarian cancer
|At a glance||Clinical trials|
|What is maintenance therapy?||Guidelines|
|What is first-line treatment?||Questions for your doctor|
|What does this mean for me?||Resources and reference|
This update is about:
On April 29, 2020, the U.S. Food and Drug Administration approved Zejula, (niraparib) as a first-line maintenance therapy for women with advanced ovarian cancer who have had a complete or partial response to chemotherapy. Zejula is a type of targeted therapy known as a PARP inhibitor. This approval applies to women both with, and women without a BRCA mutation.
Maintenance therapy is a type of treatment that is given after chemotherapy treatment has been completed to try to keep the cancer from returning. The goal of maintenance therapy is to extend the length of time before a new recurrence emerges or even to turn a temporary remission into a long-term cure. Two types of agents—PARP inhibitors and bevacizumab—have been FDA approved for use as maintenance therapy in women with advanced ovarian, fallopian tube and primary peritoneal cancer.
First-line treatment or therapy is the first treatment given for a disease such as cancer. Second-line treatments are used if the cancer doesn’t respond to first-line treatment or the cancer returns.
After a woman has been diagnosed with ovarian cancer, first-line treatment is usually several months of chemotherapy. If her cancer responds well to treatment, she may stop treatment or begin maintenance therapy, unless her cancer comes back. If her cancer comes back, she will receive second-line treatment which maybe a new course of chemotherapy or another type of treatment. If her cancer does not respond, or comes back again, the following treatment would be called third-line.
Why is this approval important?
Treatment of ovarian cancer remains a challenge. Most ovarian cancers respond well to chemotherapy; however, the majority will recur within five years. Until now, PARP inhibitors were only FDA approved for the following situations:
- As treatment for recurrent advanced ovarian cancer in women with a BRCA1 or BRCA2 mutation (found through genetic testing or tumor biomarker testing) who have received two or more previous lines of treatment
- As maintenance therapy for women with a BRCA1 or BRCA2 who have completed first-line (or higher) chemotherapy
- As maintenance therapy for women without a BRCA1 or BRCA2 mutation who completed at least second-line (or higher) chemotherapy.
This is the first FDA approval that allows women with advanced ovarian cancer without a BRCA mutation to use a PARP inhibitor as maintenance therapy after first-line treatment.
FDA approval of Zejula was based on previous research from the PRIMA trial, which we reported in this XRAY review.
PRIMA looked at whether Zejula was safe and effective as maintenance therapy after a response to chemotherapy (before recurrence) in women with newly diagnosed ovarian cancer:
- Women who received Zejula after completing chemotherapy survived longer without their cancer coming back than women who received placebo after completing chemotherapy. This is known as progression-free survival. Women who received Zejula as maintenance therapy after completing treatment:
- had an average progression-free survival time of almost 14 months compared to 8 months for patients who received a placebo after completing treatment.
- had an overall survival rate after two years rate of 84 percent, compared to 77 percent for patients who received a placebo.
- Zejula caused severe, but not life-threatening side effects in 65 percent of patients enrolled in the study. The most common side effects seen with Zejula include:
- low blood counts (e.g., anemia, low platelet count and low white blood cell count)
- abdominal pain
Low blood cell counts were managed by reducing the dose of Zejula or taking a break from treatment.
If you have been diagnosed with advanced ovarian cancer and you have had a complete or partial response to chemotherapy, you may want to talk to your doctor about maintenance therapy with Zejula or another PARP inhibitor.
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This article is relevant for:
People with advanced ovarian cancer who have had a complete or partial response to chemotherapy
This article is also relevant for:
Ovarian cancer survivors
People with a genetic mutation linked to cancer risk
Women under 45
Women over 45
Be part of XRAY:
- Is maintenance therapy with Zejula anoption for my ovarian cancer?
- If Zejula is not an option for me right now, might it be an option in the future?
- What side effects might I experience with this treatment?
- If I have serious side effects, will I need to stop treatment?
- Are any other agents available to treat my cancer?
NCT03522246: A Study in Ovarian Cancer Patients Evaluating Rucaparib and Nivolumab as Maintenance Treatment Following Response to Front-Line Platinum-Based Chemotherapy (ATHENA). ATHENA is a study for women who are newly diagnosed with ovarian cancer. The goal of ATHENA is to look at whether giving maintenance therapy with different agents improves outcomes for women who have completed front-line treatment.
NCT02855944. ARIEL4: A Study of Rucaparib Versus Chemotherapy BRCA Mutant Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Patients. ARIEL4 is a treatment study for women with relapsed, high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer who have a BRCA1 or BRCA2 mutation. ARIEL4 is designed to evaluate rucaparib against standard of care chemotherapy in women who have had at least two prior chemotherapy regimens.
- NCT03955471. A study comparing platinum-based therapy with a TSR-042 and niraparib versus standard of care platinum-based therapy as first-line treatment of Stage III or IV ovarian cancer. This study will look at the efficacy and safety of a combination of niraparib and TSR-042 (Dostarlimab), a targeted therapy in patients with advanced ovarian cancer without a known BRCA mutation who have platinum-resistant disease and who have also been previously treated with bevacizumab (Avastin).
- NCT03718091: A Non-Randomized Phase II Research Study of M6620 (VX-970) in Selected Solid Tumors to Inhibit the ATR Enzyme. This clinical trial is studying how well a targeted therapy that blocks an enzyme called ATR works in treating patients with advanced solid tumors, including ovarian cancer. The study is open to people with a BRCA1, BRCA2, or ATM mutation. The study is open to people who have previously received treatment with a PARP inhibitor.