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PARPi Indications in OC
Current PARP Inhibitor Indications for Advanced Ovarian Cancer

Released: February 02, 2024

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Key Takeaways
  • FDA approvals and guideline recommendations for PARP inhibitors (eg, niraparib, olaparib, and rucaparib) as maintenance therapy for advanced ovarian cancer have evolved recently.
  • Although PARP inhibitor indications are very similar, other factors—including BRCA1/2 or HRD status and previous bevacizumab use—may affect treatment recommendations.

During the past couple of years, the use of PARP inhibitors for the treatment of advanced ovarian cancer has evolved and is dramatically changing the treatment landscape. In this commentary, I take a brief look at the current data and clinical relevance of these agents.

Considerations for BRCA Testing
Every patient who is diagnosed with ovarian cancer should undergo germline panel testing for BRCA mutations and should be seriously considered for tumor somatic testing. In most cancer centers, after patients are diagnosed, they are seen by a genetic counselor. Oncology societies and clinical guidelines also recommend tumor somatic testing for BRCA1/2 mutations. Germline testing may be important for cascade testing of family members if the patient has been identified to carry a germline BRCA1/2 mutation. Knowing both germline and somatic BRCA testing results helps determine the appropriate use of a PARP inhibitor in either the newly diagnosed or recurrent disease setting. In regard to diagnostic testing for homologous recombination deficiency (HRD), patients may receive the MyChoice test to expand the clinical utility of PARP inhibitors beyond patients with BRCA1/2 status.

PARP Inhibitors and Current Indications
Currently, 3 PARP inhibitors—olaparib, rucaparib, and niraparib—are approved for maintenance treatment of newly diagnosed or recurrent ovarian cancer.

Niraparib Maintenance
Niraparib is approved as frontline maintenance treatment in patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer with a complete or partial response to first-line platinum-based chemotherapy. Clinical guidelines also suggest maintenance therapy with niraparib plus bevacizumab (in patients with intolerance to olaparib), and if bevacizumab previously was used together with primary treatment (Table 1). In the recurrent setting, niraparib is approved as maintenance treatment of patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer with deleterious/suspected deleterious germline BRCA mutation (based on an FDA-approved test) with a complete or partial response to platinum-based chemotherapy. Of note, PARP inhibitor maintenance treatment in patients with recurrent disease is recommended by clinical guidelines only if a PARP inhibitor was not previously used and/or disease has not progressed while the patient was receiving previous PARP inhibitor treatment (Table 2).

Olaparib
Olaparib is approved as frontline maintenance treatment in patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer and deleterious/suspected deleterious germline or somatic BRCA mutation (based on an FDA-approved test) who have achieved a complete or partial response to platinum-based chemotherapy. Olaparib also is approved as frontline maintenance treatment in combination with bevacizumab in patients with HRD-deficient—defined as the presence of deleterious/suspected deleterious BRCA mutation and/or genomic instability based on an FDA-approved test—advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer after complete or partial response to first-line platinum-based chemotherapy given with first-line bevacizumab. Olaparib also can be used as maintenance treatment in patients with recurrent ovarian cancer with deleterious/suspected deleterious germline or somatic BRCA mutation who have achieved a complete or partial response to platinum-based chemotherapy.

Rucaparib
Last but not least, rucaparib is approved only as maintenance treatment of patients with recurrent BRCA-mutated ovarian cancer in complete or partial response to platinum-based chemotherapy. However, clinical guidelines also recommend frontline maintenance with rucaparib (regardless of BRCA or HRD mutational status). These guideline recommendations are based on data from the ATHENA-MONO clinical trial evaluating maintenance rucaparib vs placebo in patients with stage III-IV ovarian cancer who underwent cytoreductive surgery and who achieved a complete or partial response after completing 4-8 cycles of frontline platinum-doublet chemotherapy.

PARP Inhibitors No longer Indicated as Single-Agent Treatment for Recurrent Ovarian Cancer
Based on recent data from the ARIEL-4 (rucaparib) and SOLO-3 (olaparib) trials, which demonstrated worse survival outcomes with rucaparib or olaparib vs chemotherapy in patients with advanced ovarian cancer and ≥2 previous lines of chemotherapy, the FDA withdrew this indication for rucaparib, and subsequently drug manufacturers for olaparib and niraparib also removed their indication in this setting. Current guidelines also no longer recommend single-agent PARP inhibitor treatment for patients with recurrent ovarian cancer.

Choosing the Right PARP Inhibitor for the Right Patient
Of importance, all 3 PARP inhibitors approved for the treatment of ovarian cancer appear to have very similar efficacy profiles. Broadly speaking, response rates, progression-free survival, and other outcomes are comparable among PARP inhibitors, as seen in clinical trials investigating maintenance therapy. So, healthcare professionals may choose the optimal agent based on other factors, such as toxicity profiles; each of these PARP inhibitors has specific toxicity mitigation strategies.

Your Thoughts?
What are your thoughts or questions on the current indications for the use of PARP inhibitors in patients with advanced newly diagnosed or recurrent ovarian cancer? Answer the polling question and join the conversation by leaving a comment.

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How often do you request or verify BRCA1/2 and HRD testing for your patients with ovarian cancer?

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