Update: PARP inhibitors withdrawn as third-line or later treatment for recurrent ovarian cancer

Contents

UPDATE AT A GLANCE

What is this update about?

Manufacturers of PARP inhibitors used to treat ovarian cancer have withdrawn their applications to treat advanced, recurrent ovarian cancer after three or more lines of treatment. This change does not affect approvals for PARP inhibitors that are used for maintenance therapy in ovarian cancer, and it does not change approvals for treating breast, pancreatic, prostate and other cancers.

Why is this update important?

Treatment options for recurrent ovarian cancer are limited. Until recently, three PARP inhibitors were approved for treating advanced ovarian cancer in women who experienced recurrence or progression after three or more lines of chemotherapy. Based on the results of the ARIEL4 clinical trial, FDA approvals for all three PARP inhibitors have been withdrawn for this indication.

Although the early results from the ARIEL4 trial supported the use of the PARP inhibitors instead of chemotherapy as a treatment option for recurrent disease, longer-term data on overall survival data indicate that chemotherapy treatment is more beneficial than PARP inhibitors for this indication.

What are PARP inhibitors?

PARP inhibitors are a type of targeted therapy that was developed to treat cancers in people with a BRCA1 or BRCA2 mutation. They were first approved to treat advanced ovarian cancer in people with one of these mutations who had received multiple lines of treatment. Since then, research has expanded the use of PARP inhibitors to additional situations.

Indications for PARP inhibitors

Currently, four PARP inhibitors are approved to treat breast, ovarian, pancreatic and prostate cancers. Indications for approved PARP inhibitors vary by cancer type, whether a person has an inherited mutation found by genetic testing or a cancer that has a mutation found by tumor testing. The current approvals for PARP inhibitors are summarized by cancer and indication here.

Study findings

Early progression-free survival data

Previous results of the ARIEL4 trial supported the use of the PARP inhibitor Rubraca (rucaparib) as an alternative to chemotherapy for patients with recurrent ovarian cancer who have a BRCA mutation. Results reported in 2021 showed that as a third-line treatment, Rubraca improved progression-free survival by almost two months compared to chemotherapy. Progression-free survival was:

• 7.4 months for patients taking Rubraca.
• 5.7 months for patients who had chemotherapy.

When these initial progression results were reported, the analysis of overall survival data had not yet been completed.

Updated overall survival data

In September 2022, the overall survival data from ARIEL4 was published. It showed that chemotherapy was a more beneficial treatment than Rubraca:

• Overall survival was 19.4 months for people taking Rubraca.
• Overall survival was 25.4 months for people who had chemotherapy.
• Overall survival was improved by chemotherapy in three participant groups:
  • For participants with platinum-resistant disease, overall survival was:
    • 14.2 months for patients taking Rubraca.
    • 22.2 months for patients who had chemotherapy.
  • Among participants with partially platinum-sensitive disease, overall survival was:
    • 21.1 months for patients taking Rubraca.
    • 23.2 months for patients who had chemotherapy.
  • Among participants with fully platinum-sensitive disease, overall survival was:
    • 36.3 months for patients taking Rubraca.
    • 47.2 months for patients who had chemotherapy.

What does this mean for me?

Given these overall survival outcomes, the companies that manufacture Rubraca, Zejula and Lynparza voluntarily withdrew their indications for third-line or higher treatment of recurrent ovarian cancer. However, depending on the patient, these drugs may still be used off-label for this indication. Importantly, this update does not apply to PARP inhibitors used as maintenance therapy after ovarian cancer treatment has been completed or to certain other indications.

Reference

Oza AM, Lisyanskaya AS, Fedenko AA, et al. Overall survival results from ARIEL4: A phase III study assessing rucaparib vs chemotherapy in patients with advanced, relapsed ovarian carcinoma and a deleterious BRCA1/2 mutation. Presented at ESMO 2022; September 9-13, 2022. Abstract 518O.

Disclosure: FORCE receives funding from industry sponsors, including companies that manufacture cancer drugs, tests and devices. All XRAYS articles are written independently of any sponsor and are reviewed by members of our Scientific Advisory Board prior to publication to assure scientific integrity.

Share your thoughts on this XRAY review by taking our brief survey.  

posted 10/4/22