AstraZeneca and Merck & Co (known as MSD outside the US and Canada) announced that the Japanese Ministry of Health, Labour and Welfare has approved Lynparza (olaparib) tablets (300mg twice daily) for use as a maintenance therapy for patients with platinum-sensitive relapsed ovarian cancer, regardless of their BRCA mutation status, who responded to their last platinum-based chemotherapy.
Lynparza is the first poly ADP-ribose polymerase (PARP) inhibitor to be approved in Japan.
Dave Fredrickson, Executive Vice President, Head of the Oncology Business Unit at AstraZeneca, said: “We are proud to bring this important first-in-class treatment to women with platinum-sensitive relapsed ovarian cancer in Japan who currently have very few treatment options. The trials show that with Lynparza maintenance therapy, women with ovarian cancer can live longer without their disease worsening and Lynparza is well tolerated.”
Roy Baynes, Senior Vice President and Head of Global Clinical Development, Chief Medical Officer, MSD Research Laboratories, said: “Today’s decision is significant for Lynparza and, more importantly, for Japanese patients living with advanced ovarian cancer. Our global collaboration with AstraZeneca reinforces how our joint efforts can advance science for patients, and we look forward to working together to explore the potential of Lynparza across multiple tumour types.”
The approval was granted on the basis of two randomised trials of Lynparza maintenance therapy for platinum-sensitive relapsed ovarian cancer, SOLO-2 and Study 19.
Summary of key efficacy results from randomised trials:
|Analysis||Reduction in the risk of disease progression or death (PFS)||Reduction in the risk of death (OS)|
|Lynparza||70% (HR 0.30 [95% CI, 0.22-0.41], P<0.0001; median 19.1 vs 5.5 months by investigator-assessed analysis)||Data not yet mature|
|Lynparza||65% (HR 0.35 [95% CI, 0.25-0.49], P<0.0001;
median 8.4 vs 4.8 months)
|27% (HR 0.73 [95% CI, 0.55-0.95];
median 29.8 vs 27.8 months)
*PSR = Platinum-sensitive recurrent ovarian cancer
In SOLO-2, the most common adverse drug reactions (≥20%) of any grade reported in patients in the Lynparza arm were nausea (66.7%), anaemia (39.0%), fatigue (29.7%), vomiting (25.6%), asthenia (24.1%) and dysgeusia (23.1%).
In Study 19, the most common adverse drug reactions (≥20%) of any grade reported in patients in the Lynparza arm were nausea (64.0%), fatigue (43.4%) and vomiting (21.3%).
Lynparza is also currently under review for use in unresectable or recurrent BRCA-mutated, HER2-negative breast cancer in Japan, with a decision expected in the second half of 2018 based upon a priority review.
About Ovarian Cancer in Japan
Worldwide, ovarian cancer is the seventh most commonly diagnosed cancer and the eighth-most-common cause of cancer deaths in women. In Japan, more than 9,000 women are diagnosed with ovarian cancer every year and the five-year survival rate is 58%, the lowest among all gynaecological cancers.
In 2012, 4,758 women with ovarian cancer died, which represents one out of every two patients. As there is no cure for relapsed ovarian cancer, the primary aim of treatment is to slow progression of the disease for as long as possible and improving or maintaining a patient’s quality of life.
SOLO-2 was a Phase III, randomised, double-blinded, multicentre trial designed to determine the efficacy of Lynparza tablets as a maintenance monotherapy compared with placebo, in patients with platinum-sensitive, relapsed or recurrent gBRCA-mutated ovarian, fallopian tube and primary peritoneal cancer.
The trial, conducted in collaboration with the European Network for Gynaecological Oncological Trial Groups (ENGOT) and Groupe d’Investigateurs National pour l’Etude des Cancers de l’Ovaire et du sein (GINECO), randomised 295 patients with documented germline BRCA1 or BRCA2 mutations who had received at least two prior lines of platinum-based chemotherapy and were in complete or partial response. Eligible patients were randomised to receive 300mg Lynparza tablets twice daily or placebo tablets twice daily.
About Study 19
Study 19 was a Phase II, randomised, double-blinded, placebo-controlled, multicentre trial, which evaluated the efficacy and safety of Lynparza compared with placebo in relapsed, high-grade serous ovarian cancer patients.
The trial randomised 265 patients regardless of BRCA mutation status and who had completed at least two courses of platinum-based chemotherapy and their most recent treatment regimen. Eligible patients were randomised to receive Lynparzamaintenance monotherapy at a dose of 400mg per day or matching placebo.
About Lynparza (olaparib)
Lynparza is a first-in-class poly ADP-ribose polymerase (PARP) inhibitor and the first targeted treatment to potentially exploit tumour DNA damage response (DDR)-pathway deficiencies to preferentially kill cancer cells. Specifically, in vitro studies have shown that Lynparza-induced cytotoxicity may involve inhibition of PARP enzymatic activity and increased the formation of PARP-DNA complexes, resulting in DNA damage and cancer cell death.
Lynparza is being investigated in a range of DDR-deficient tumour types and is the foundation of AstraZeneca’s industry-leading portfolio of compounds targeting DDR mechanisms in cancer cells.