Xagena.net - Update in Medicine

Olaparib ( Lynparza ) met primary endpoint of progression-free survival in women with BRCA-mutated advanced ovarian cancer and showed a safety profile in SOLO-1 trial consistent with previous trials.
Olaparib is the only PARP inhibitor to demonstrate significant activity in the 1st-line maintenance setting.

Women with BRCA-mutated ( BRCAm ) advanced ovarian cancer treated 1st-line with Olaparib maintenance therapy had a statistically-significant and clinically-meaningful improvement in progression-free survival compared to placebo.

SOLO-1 is a phase III randomised, double-blinded, placebo-controlled, multicentre trial to evaluate the efficacy and safety of Olaparib tablets as 1st-line maintenance monotherapy compared with placebo, in patients with BRCAm advanced ovarian cancer.
The trial randomised 391 patients with a deleterious or suspected deleterious BRCA1 or BRCA2 mutation who were in clinical complete or partial response following Platinum-based chemotherapy.
Eligible patients were randomised ( 2:1 ) to receive Olaparib 300mg tablets twice daily or placebo tablets twice daily.
The primary endpoint was progression-free survival and key secondary endpoints included time to second disease progression or death and overall survival.

BRCA1 and BRCA2 are human genes that produce proteins responsible for repairing damaged DNA and play an important role in maintaining the genetic stability of cells.
When either of these genes is mutated, or altered, such that its protein product either is not made or does not function correctly, DNA damage may not be repaired properly and cells become unstable.
As a result, cells are more likely to develop additional genetic alterations that can lead to cancer.

Worldwide, ovarian cancer is the seventh most common cancer and the eighth leading cause of cancer death in women.
The five-year survival rate for ovarian cancer worldwide is 30-40%.
In 2012, there were nearly 239,000 new cases diagnosed and around 152,000 deaths.
For newly diagnosed advanced ovarian cancer, the primary aim of treatment is to delay progression of the disease for as long as possible and maintain the patient’s quality of life with the intent of achieving complete remission or cure.

Olaparib was the first-in-class PARP inhibitor and the first targeted treatment to potentially exploit DNA damage response ( DDR ) pathway deficiencies, such as BRCA mutations, to preferentially kill cancer cells.
Specifically, in vitro studies have shown that Olaparib-induced cytotoxicity may involve inhibition of PARP-enzymatic activity and increased formation of PARP-DNA complexes, resulting in DNA damage and cancer cell death.
Olaparib is being tested in a range of DDR-deficient tumour types.

Lynparza is approved for advanced ovarian cancer and metastatic breast cancer. ( Xagena )

Source: AstraZeneca, 2018