AstraZeneca and Merck & Co announced that the US Food and Drug Administration (FDA) has granted approval for the PARP inhibitor, Lynparza (olaparib).
The approval is as follows:
- New use of Lynparza as a maintenance treatment for recurrent, epithelial ovarian, fallopian tube or primary peritoneal adult cancer who are in response to platinum-based chemotherapy, regardless of BRCA status
- New use of Lynparza tablets (2 tablets twice daily) as opposed to capsules (8 capsules twice daily)
- Lynparza tablets also now indicated (conversion from the current accelerated approval) for the use in patients with deleterious or suspected deleterious germline BRCA-mutated advanced ovarian cancer, who have been treated with three or more prior lines of chemotherapy.
“Physicians have almost three years of clinical experience with Lynparza on the market and we are now pleased to bring this important medicine, in a new tablet formulation, to a broader group of women. Today’s approvals validate more than 10 years of dedicated research behind Lynparza, the world’s first PARP inhibitor, which now provides oncologists with the greater flexibility for use in terms of treatment settings. It builds on our recently-announced collaboration with Merck, which aims to further increase the number of treatment options available to patients,” said Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer, AstraZeneca.
Two randomized trials supported the new approvals and the conversion of accelerated approval to full approval which was originally based on a single-arm trial:
- SOLO-2 (n=295) confirmed the benefit of Lynparza in germline BRCA-mutated (gBRCAm) patients, demonstrating a 70% reduced risk of disease progression or death (HR 0.30 [95% CI, 0.22-0.41], P<0.0001) and improved progression-free survival (PFS) to 19.1 vs 5.5 months for placebo by investigator-assessed analysis.
- Study 19 (n=265) showed that Lynparza reduced the risk of disease progression or death by 65% and improved PFS compared with placebo in patients of any BRCA status (HR 0.35 [95% CI, 0.25-0.49], P<0.0001; median PFS of 8.4 months vs 4.8 months for placebo). Additionally, patients in Study 19, treated with Lynparza as a maintenance therapy, had a median overall survival (OS) of 29.8 months vs 27.8 months for placebo (HR 0.73 [95% CI, 0.55-0.95]).Table 1. Summary of key efficacy results from randomised trials:
The most-common adverse events reported in 20% or more of patients across the SOLO-2 trial in the Lynparza arm were anaemia (44%), nausea (76%), vomiting (37%), diarrhoea (33%), fatigue/asthenia (66%), decreased appetite (22%), headache (25%), and dysgeusia (27%). The most-common Grade 3 or 4 adverse events were anaemia (20%), nausea (2.6%), vomiting (2.6%), diarrhoea (1.0%), fatigue/asthenia (4.1%), and headache (0.5%). Discontinuation of Lynparza resulting from adverse events was seen in 11% of patients. Dose interruptions of Lynparza due to an adverse reaction of any grade was 45%. Dose reductions of Lynparza due to an adverse reaction was 25%.
The most-common adverse events reported in 20% or more of patients across the Study 19 trial in the Lynparza arm were anaemia (23%), nausea (71%), vomiting (35%), diarrhoea (27%), fatigue (including asthenia) (63%), decreased appetite (21%), and headache (21%). The most-common Grade 3 or 4 adverse events were anaemia (7.4%), nausea (2.2%), vomiting (2.2%), diarrhoea (2.2%), and fatigue (including asthenia) (8.8%). Discontinuation of Lynparza resulting from adverse events was seen in 4% of patients. Dose interruptions of Lynparza due to an adverse reaction of any grade was 25%. Dose reductions of Lynparza due to an adverse reaction was 15%.
Lynparza was first approved under the FDA’s Accelerated Approval programme in December 2014, as a capsule formulation, making it the first poly ADP-ribose polymerase (PARP) inhibitor approved. Since then, more than 3,000 advanced ovarian cancer patients have been treated with Lynparza capsules in its approved indication.