Lynparza (olaparib) has been approved in Japan as a maintenance treatment for women with advanced ovarian cancer who responded to a first-line chemotherapy regimen containing bevacizumab, AstraZeneca and Merck announced in a press release.
The approval, for patients whose cancer is positive for homologous recombination deficiency (HRD), is based on data from the PAOLA-1 Phase 3 trial (NCT02477644), in which oral Lynparza significantly extended the time patients lived without disease worsening by about 1.5 years.
Regulators in Japan also approved Lynparza for two other cancer indications: people with metastatic castration-resistant prostate cancer (mCRPC) who carry mutations in the BRCA DNA repair genes, and as a maintenance treatment for BRCA-mutated inoperable pancreatic cancer.
“For patients in Japan diagnosed with each of these types of cancer, there are very few treatment options,” said Roy Baynes, MD, PhD, senior vice president, head of global clinical development, and chief medical officer at Merck Research Laboratories.
“Approvals for treatments such as Lynparza … enable us to advance this evolving era of personalized medicine and change how these cancers are treated,” added Baynes.
Lynparza, an oral treatment developed by AstraZeneca and Merck (known as MSD outside North America), works by blocking the activity of PARP enzymes, which are involved in DNA repair. The therapy renders cancer cells more vulnerable to DNA damage, limiting their ability to grow and survive.
HRD-positive tumors — those carrying mutations in the BRCA genes and/or exhibiting genomic instability (a high frequency of mutations within the genome) — often rely on the PARP enzyme to repair their DNA. People with these tumors often respond better to PARP inhibitors such as Lynparza.
PAOLA-1 involved 806 patients, all with at least partial responses to first-line platinum-based chemotherapy plus bevacizumab. They were randomly assigned them to either Lynparza (537 women) or a placebo (269 women), give twice daily for up to two years.
All participants were treated with an intravenous (into-the-vein) infusion of bevacizumab, given every three weeks for 15 months.
It met its main goal, showing a Lynparza plus bevacizumab combination extended the time lived without signs of disease progression.
But benefits were particularly evident among the 387 women with HRD-positive tumors, whose likelihood of disease progression or death changed from a median 17.7 months with bevacizumab alone to 37.2 months with the combination — representing a 67% risk reduction.
The effect was more modest in women with HRD-positive tumors and without BRCA mutations, but their median progression-free survival was also significantly extended with Lynparza, from 16.6 to 28.1 months.
Notably, in women with HRD-positive tumors who required a second line of therapy after progressing on Lynparza, the treatment also lowered the risk of disease progression or death while on that second therapy. It fell by 44% in those whose tumors carried BRCA mutations, and by 40% in those lacking such mutations.
“These three approvals … further underline the critical importance of biomarker testing at diagnosis, which helps physicians determine a course of treatment tailored to their individual patients to substantially delay disease progression,” said Dave Fredrickson, executive vice president of AstraZeneca’s oncology business unit.
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