Maintenance therapy with the PARP inhibitor Lynparza (olaparib) added to Avastin (bevacizumab) resulted in a significant and clinically meaningful delay in cancer progression in patients with advanced stage III-IV ovarian cancer  according to the results of the phase 3 PAOLA-1/ENGOT-ov25 study presented at the European Society for Medical Oncology (ESMO) Congress 2019. (1)

About Lynparza (olaparib)

Lynparza is a first-in-class PARP inhibitor and the first precision cancer medicine to block DNA damage response (DDR) in cancers harboring a deficiency in homologous recombination repair (HRR), such as mutations in BRCA1 and/or BRCA2.

The PARP enzyme plays a role in DNA repair, including the repair of DNA damage from chemotherapy. Precision cancer medicines that target and inhibit this enzyme may contribute to cancer cell death and increased sensitivity to chemotherapy and are called PARP inhibitors. By blocking this enzyme, DNA inside the cancerous cells is less likely to be repaired, leading to cell death and possibly a slow-down or stoppage of tumor growth. Doctors theorized that the addition of DNA-damaging agents, such as alkylating agents like temozolomide, may enhance the activity of PARP inhibitors and evaluated the combination in an early phase clinical trial to evaluate the feasibility of the combination.

Paola Clinical Trial

The clinical trial enrolled 537 women with newly diagnosed ovarian cancer who had been treated with platinum-based chemotherapy plus Avastin. Patients were then additionally treated with maintenance therapy consisting of Lynparza tablets plus Avastin or Avastin alone and directly compared.

Overall the progression-free survival was 22.1 months for Lynparza + Avastin compared with 16.6 months for Avastin alone demonstrating that the combination benefits all ovarian cancer patients to some extent.

PARP inhibitors are known to have their greatest impact in women with BRCA or homologous recombination deficiency (HRD) and sub-group analyses of the trial confirmed this.

  • Patients with BRCAmutations treated with Lynparza had a median progression-free survival of 37.2 months compared with 21.7 months for Avastin alone.
  • Patients with HRD had a median progression-free survival of 37.2 months with Lynparza plus Avastin compared to 17.7 months for Avastin alone.

Lynparza and Avastin maintenance therapy appears to benefit most patients with advanced ovarian cancer and all women with ovarian cancer should ensure they undergo testing for BRCA, HRD and other mutations that can help determine the role of PARP maintenance therapy.

References

  1. Ray-Coguard IL, Pautier P, Pignata S, et al. Phase III PAOLA-1/ENGOT -ov25trial: Olaparib plus bevacizumab (bev) as maintenance therapy in patients (pts) with newly diagnosed, advanced ovarian cancer (OC) treated with platinum-based chemotherapy (PCh) plus bev. Presented at: European Society of Medical Oncology (ESMO) Congress 2019; September 27-October 1, 2019: Barcelona, Spain. Abstract LBA2_PR.
  2. European Society of Medical Oncology (ESMO). Ovarian cancer: more women benefit from maintenance combined targeted therapy. Published September 28, 2019.

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