AstraZeneca plc (LON: AZN) and MSD Inc., Kenilworth, N.J., US (MSD: known as Merck & Co., Inc. inside the US and Canada) have today announced that the European Commission (EC) has approved Lynparza (olaparib) as a 1st-line maintenance treatment for women with BRCA-mutated advanced ovarian cancer.
The licensed indication is as a maintenance treatment of adult patients with advanced (FIGO stages III and IV) BRCA1/2-mutated (germline and/or somatic) high-grade epithelial ovarian, fallopian tube or primary peritoneal cancer who are in response (complete or partial) following completion of 1st-line platinum-based chemotherapy.
Dave Fredrickson, Executive Vice President, Oncology Business Unit, said:
“This approval sets the stage for a new standard of care in the EU for women with ovarian cancer and a BRCA mutation. The goals of front-line therapy have always been long-term remission and even cure, yet currently 70% of patients relapse within three years of initial treatment. The progression-free survival benefit of Lynparza observed in SOLO-1 represents a major step forward in our ambition to help transform patient outcomes.”
Roy Baynes, Senior Vice President and Head of Global Clinical Development, Chief Medical Officer, MSD Research Laboratories, said:
“In SOLO-1, Lynparza demonstrated clinically-meaningful results with a 70% reduction in the risk of disease progression or death in the first-line maintenance treatment of patients with BRCAm advanced ovarian cancer. Merck and AstraZeneca are committed to improving outcomes for people with cancer and we will work to bring this new option to women in the EU, many of whom have historically poor outcomes, as quickly as possible.”
The EC approval was based on data from the pivotal Phase III SOLO-1 trial which tested Lynparza as maintenance monotherapy compared with placebo in patients with BRCAm advanced ovarian cancer following 1st-line platinum-based chemotherapy. Results announced in October 2018 at 40.7 months of follow-up showed the median time of progression for patients treated with Lynparza had not yet been reached vs. 13.8 months for those on placebo (HR 0.30 [95% CI, 0.23-0.41], p<0.001).
This is the third indication for Lynparza in the EU. AstraZeneca and MSD are exploring additional trials in ovarian cancer, including the ongoing Phase III PAOLA-1 trial, which is testing Lynparza in combination with bevacizumab as a 1st-line maintenance treatment for women with newly-diagnosed, advanced, stage IIIB-IV high grade serous or endometrioid ovarian cancer, regardless of BRCA status.
SOLO-1 was a Phase III, randomised, double-blinded, placebo-controlled, multi-centre trial to evaluate the efficacy and safety of Lynparza tablets (300mg twice daily) as a maintenance monotherapy compared with placebo in patients with BRCAm advanced ovarian cancer following first-line platinum-based chemotherapy. The trial randomised 391 patients with a deleterious or suspected deleterious germline or somatic BRCA1 or BRCA2 mutation who were in clinical complete or partial response following platinum-based chemotherapy.
Patients were randomised (2:1) to receive Lynparza or placebo for up to two years or until disease progression. Patients who had a partial response at two years were permitted to stay on therapy at the investigator’s discretion. The primary endpoint was progression-free survival (PFS) and key secondary endpoints included time to second disease progression or death, time to first subsequent treatment and overall survival.
The data were presented on 21 October 2018, at the Presidential Symposium of the ESMO (European Society for Medical Oncology) 2018 Congress in Munich, Germany and published simultaneously online in The New England Journal of Medicine.
Summary of PFSi,ii
|Lynparza (n=260)||Placebo (n=131)|
|Number of patients with event (%)iii||102 (39)||96 (73)|
|Median PFS (in months)||Not reached||13.8|
|Hazard ratio (95% CI)||0.30 (0.23-0.41)||0.30 (0.23-0.41)|
ii Median (interquartile range) duration of follow-up 40.7 months (34.9-42.9) for Lynparza and 41.2 months (32.2-41.6) for placebo.
iii Analysis was done at 50.6% maturity.
The SOLO-1 safety profile was in line with that observed in prior clinical trials. The most common adverse events (AEs) ≥ 20% were nausea (77%), fatigue (63%), vomiting (40%), anaemia (39%) and diarrhoea (34%). The most common ≥ Grade 3 AEs were anaemia (22%) and neutropenia (9%). Some 71% of patients on Lynparza remained on the recommended starting dose. Additionally, 88% of patients on Lynparza continued treatment without an AE-related discontinuation.
Under the oncology collaboration with MSD and following this new approval for Lynparza, AstraZeneca will receive $30m as Ongoing Collaboration Revenue, anticipated to be booked by the Company during the second quarter of 2019.