AstraZeneca and Merck & Co. have entered into a rewarding period in their partnership to develop and commercialise Lynparza (olaparib), as another Phase III trial for their targeted therapy has been reported to meet the primary endpoint in first-line treatment of advanced ovarian cancer.
Lynparza, Avastin combination
The outcome of the PAOLA-1 trial supports the benefit of adding Lynparza to the standard of care (SOC) maintenance therapy with Avastin (bevacizumab), which will entail a new standard first-line maintenance treatment for patients with ovarian cancer who show a response to chemotherapy.
Lynparza, the first-to-market and the leader in its class, is a poly ADP ribose polymerase (PARP) inhibitor that was introduced to treat ovarian cancer in 2014, initially in the recurrent disease treatment setting. However, the drug eventually moved up to front-line treatment in late 2018, following the successful results from the earlier SOLO-1 trial. In this trial, Lynparza as a single-agent maintenance therapy demonstrated a progression-free survival benefit in the newly-diagnosed and advanced ovarian cancer patients who were confirmed with deleterious BRCA1/2 mutations and were responsive to first-line of chemotherapy.
The significance of the PAOLA-1 trial is immense, mainly because even patients without deleterious BRCA1/2 mutations might be eligible for Lynparza, either as monotherapy or in combination with Avastin, which means a significantly broader patient population will have access to this drug.
Secondly, the Lynparza and Avastin combination as maintenance therapy will resemble a second leap of improvement in the front-line treatment of ovarian cancer, since the 2011 approval of Avastin in the first line as a combination with paclitaxel-carboplatin. There are other therapies, such as follow-on PARP inhibitors Zejula, and veliparib (currently in pipeline), eyeing approvals in the front-line setting.
Despite the good news, 25% to 50% of patients with advanced ovarian cancer will not be eligible for Lynparza. Furthermore, the added toxicity and cost of using Lynparza with the SOC, as well as the subgroup analysis from the PAOLA-1 trial and physician experience in patients without deleterious BRCA1/2 mutations, will critically determine the use and uptake of the drug in the long run.
Nonetheless, with this development, Lynparza appears to have strengthened its position in the front-line treatment setting for ovarian cancer. Furthermore, GlobalData expects that the highly-anticipated combination of Avastin and Lynparza will become a new standard of care in ovarian cancer patients who respond to chemotherapy and will considerably enhance survival outcomes.
Globaldata (2019). Ovarian Cancer – Opportunity Analysis and Forecast to 2028 (to be published)