Update: FDA approves the PARP inhibitor olaparib (Lynparza) in combination with bevacizumab (Avastin) as maintenance therapy for some women with advanced ovarian cancer

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Contents

At a glance                  Questions for your doctor
What does this mean for me? In depth            
Clinical trials Limitations
Guidelines Resources and reference


APPROVAL AT A GLANCE

What does the FDA approval say?

On May 8, 2020, the Food and Drug Administration approved the use of the PARP inhibitor olaparib (Lynparza) in combination with bevacizumab (Avastin) as a first-line maintenance therapy for women with advanced ovarian cancer who have had a complete or partial response to chemotherapy.

The FDA also approved a test that helps to identify women who will benefit from this combination therapy. The test measures how effectively cancer cells are able to repair DNA damage. Cancer cells that cannot repair DNA damage are more sensitive to certain types of treatment.

The test—called a “homologous recombination deficiency”, or “HRD” test—reports whether a tumor is HRD-positive or HRD-negative, based on two features of the cancer cells:

  • The presence or absence of a BRCA1 or BRCA2 tumor mutation. Tumor cells with BRCA mutations have difficulty repairing DNA damage.
  • “Genomic instability,” other DNA changes that make it difficult for the tumor cells to repair DNA damage.

HRD-positive tumors have trouble repairing DNA damage, which makes them sensitive to the Lynparza-Avastin drug combination.

Why is this FDA approval important?

Standard treatment for many advanced ovarian cancer patients includes chemotherapy plus bevacizumab (Avastin). Some women receive additional treatment known as maintenance therapy with either Avastin or a PARP inhibitor. This recent FDA approval is the first time a PARP inhibitor (Lynparza) has been approved in combination with Avastin for maintenance therapy in women with ovarian cancer.

PAOLA-1 clinical trial

FDA approval of the Lynparza-Avastin combination was based on results of the ongoing PAOLA-1 clinical trial. All participants had either a partial or a complete response to chemotherapy plus Avastin. After chemotherapy, they were placed in one of two groups:

  • One group received maintenance therapy with Lynparza and Avastin.
  • Another group received maintenance therapy with Avastin and a placebo.

After follow-up of almost 23 months, patients taking Lynparza plus Avastin had an additional 6 months of progression-free survival compared to patients taking Avastin alone.

  • Among patients with a BRCA tumor mutation, patients taking Lynparza plus Avastin had an additional 15 months of progression-free survival compared to patients taking Avastin alone.
  • Among patients whose tumors had HRD, but no BRCA mutation, patients taking Lyparza plus Avastin had an additional 11.5 months of progression-free survival compated to patients taking Avastin alone.
  • Patients with tumors that were HRD-negative showed no difference in progression-free survival between the two treatments.
  • No differences in quality-of-life scores were found between the two groups.

The most common side effects of Lynparza plus Avastin included:

  • fatigue
  • nausea
  • anemia
  • vomiting
  • diarrhea
  • urinary tract infection
  • headache
  • low white blood cell counts

This new approval expands the use of Lynparza as a maintenance therapy. It can now be prescribed in combination with Avastin as a first-line maintenance therapy for advanced ovarian cancer patients whose tumor is HRD-positive.

What is first-line treatment?

First-line treatment is the initial treatment given for a disease, such as cancer. Second-line treatments are used for cancers that return or do not respond to treatment. 

For most women diagnosed with ovarian cancer, first-line treatment usually involves surgery and several months of chemotherapy. Women whose cancer responds well to treatment may stop treatment altogether or stop treatment and start maintenance therapy

Women whose cancer comes back will receive second-line treatment, which may be a new course of chemotherapy or another type of treatment. Third-line treatment is recommended for cancers that return or do not respond to treatment.

What is maintenance therapy?

Maintenance therapy is given after chemotherapy to try to keep the cancer from returning. The goal is to extend the length of time before recurrence or to turn remission into a long-term cure.

What does this mean for me?

If you have ovarian cancer that responded to chemotherapy, you may benefit from maintenance therapy using a PARP inhibitor combined with Avastin.

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This article is relevant for:

Women with advanced ovarian cancer whose tumor has a BRCA mutation or a type of tumor marker called homologous recombination deficiency (HRD)

This article is also relevant for:

Ovarian cancer survivors

People with a genetic mutation linked to cancer risk

Women under 45

Women over 45

Platinum sensitive ovarian cancer

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Questions to Ask
  • Am I eligible for first-line maintenance therapy with a PARP inhibitor?
  • I just finished second-line chemotherapy; would I benefit from maintenance therapy?
  • I have an inherited BRCA mutation; would I benefit from a PARP inhibitor and Avastin for treatment?
  • What are the risks and benefits of taking a PARP inhibitor?
  • What are the differences between PARP inhibitors that are approved for first-line maintenance therapies?
Clinical Trials

IN-DEPTH REVIEW OF RESEARCH RELATED TO APPROVAL

PARP inhibitors are already approved for treatment and as a single-agent maintenance therapy for some ovarian cancer patients.

New FDA approval for Lynparza

On May 8, 2020, the Food and Drug Administration approved the PARP inhibitor olaparib (Lynparza) in combination with bevacizumab (Avastin) as a first-line maintenance therapy for women with advanced ovarian cancer. Specifically, it is for women who have had a complete or partial response to chemotherapy and whose tumor has a specific form of genomic instability (called homologous recombination deficiency or HRD).

Biomarker testing can be used to determine whether a tumor has this genomic instability or HRD. The test counts the number of mutations in a given piece of DNA in tumor cells. The MyChoice CDx test (Myriad Genetics) can determine whether a tumor has HRD. Genomic instability can be caused by inherited or tumor mutations in BRCA1, BRCA2 or in other genes.

PAOLA-1 clinical trial

Approval of Lynparza in combination with Avastin for maintenance therapy was based on the following preliminary results of the ongoing PAOLA-1 clinical trial:

  • After a median follow-up of 22.9 months, median progression-free survival was:
    • 22.1 months for patients taking Lynparza and Avastin.
    • 16.6 months for patients taking Avastin and placebo.
  • When analysis was limited to patients with tumor BRCA mutations, median progression-free survival was:
    • 37.2 months for patients taking Lynparza and Avastin.
    • 21.7 months for patients taking Avastin and placebo.
  • When analysis was limited to patients with tumors that only had HRD (inherited or tumor mutation in BRCA 1 or BRCA2), the median progression-free survival was:
    • 28.1 months for patients taking Lynparza and Avastin.
    • 16.6 months for patients taking Avastin and placebo .
  • Patients with tumors that were HRD-negative or of unknown HRD status showed no difference in progression-free survival between treatment arms.
  • No significant differences in quality of life scores were found between treatment arms.

What does this mean for me?

If you have ovarian cancer that responded to chemotherapy, you may benefit from maintenance therapy using a PARP inhibitor combined with Avastin.

Limitations

Participants in this study were placed into one of two groups:

  • One group received maintenance therapy with Avastin alone
  • The other group received maintenance therapy with Lynparza and Avastin.

No group received Lynparza only as maintenance therapy. The study design makes it difficult to know whether the combination of Lynparza and Avastin is better than Lynparza alone.

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