The European Medicines Agency ( EMA ) has approved Lynparza ( Olaparib ) tablets ( 300mg twice daily ) for use as a maintenance therapy for patients with Platinum-sensitive relapsed high-grade, epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete response or partial response to Platinum-based chemotherapy, regardless of BRCA status.
The EU approval was based on two randomised trials, SOLO-2 and Study 19, which showed that Lynparza reduced the risk of disease progression or death for Platinum-sensitive relapsed ovarian cancer patients compared to placebo.
In SOLO-2, the investigator-assessed analysis of progression-free survival ( PFS ) was supported with a blinded, independent, central radiological review of PFS, which showed a two-year difference in median PFS between Olaparib and placebo ( hazard ratio, HR=0.25 [ 95% CI, 0.18-0.35 ], p less than 0.0001; median 30.2 months vs 5.5 months ).
Overall survival ( OS ) data from SOLO-2 is currently immature.
In the final analysis of Study 19, with greater than five years of follow-up, the significant improvement in PFS translated into improvements in other key efficacy endpoints, regardless of BRCA status.
Additionally, the analysis showed 13% of patients treated with Lynparza remained progression-free and on therapy for five years or more years.
The most frequently observed adverse reactions across clinical trials in patients receiving Lynparza monotherapy ( greater than or equal to 10% ) were nausea, vomiting, diarrhoea, dyspepsia, fatigue, headache, dysgeusia, decreased appetite, dizziness and anaemia.
The majority of patients on Lynparza remained on the starting dose and only 6-11% of patients discontinued treatment due to an adverse event.
Approximately half of women with high grade epithelial ovarian cancer are expected to have deficiencies in homologous recombination repair ( HRR ), an important DNA damage response ( DDR ) pathway.
Mutations most often occur within one of the BRCA genes, however other gene mutations can also impact the HRR pathway.
While there are currently no routine tests to identify patients with these deficiencies beyond BRCA mutations, responsiveness to Platinum-based chemotherapy can predict sensitivity to PARP inhibition.
Lynparza, the first PARP inhibitor approved, was initially licensed in Europe as a capsule formulation for women with BRCA-mutated Platinum-sensitive relapsed ovarian cancer.
The new tablet formulation, which reduces dosing from eight capsules twice daily to two tablets twice daily, will now be available for a broader group of women with Platinum-sensitive relapsed ovarian cancer. ( Xagena )
Source: AstraZeneca, 2018