AstraZeneca and Merck & Co., Inc., known as MSD outside the United States and Canada, announced that the U.S. Food and Drug Administration (FDA) has granted approval for the PARP inhibitor, Lynparza (olaparib), 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.
Eric Pujade-Lauraine, head of the women cancers and clinical research department at Hôpitaux Universitaires Paris Centre, site Hôtel-Dieu, AP-HP and principal investigator of the SOLO-2 trial, one of the trials supporting the approval, said: “Today’s approval is welcome news for U.S. patients with ovarian cancer, who are now able to benefit from treatment with olaparib irrespective of their BRCA-mutation status. This latest regulatory milestone underscores the breadth and depth of clinical data on olaparib, and not only demonstrates its efficacy as maintenance therapy, but adds to the data presented earlier this year showing sustained quality of life for patients undergoing treatment for this serious disease.”
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 randomized trials: |
|||||||||||
Analysis |
Reduction in the risk of |
Reduction in the risk of |
|||||||||
SOLO-2 |
Lynparza |
70% (HR 0.30 [95% CI, 0.22- |
Data not yet mature | ||||||||
Placebo | |||||||||||
Study 19 |
Lynparza |
65% (HR 0.35 [95% CI, 0.25- |
27% (HR 0.73 [95% CI, |
||||||||
Placebo | |||||||||||
*PSR = Platinum-sensitive recurrent ovarian cancer |
|||||||||||
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%.
The full data from the SOLO-2 trial can be found in the July 25, 2017 publication of The Lancet Oncology.
Lynparza was first approved under the FDA’s Accelerated Approval program 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.
(Source: Business Wire)