Positive results from the phase 3 PAOLA-1 trial in women with advanced ovarian cancer. were announced.
The trial, in the first-line maintenance setting, compared Olaparib ( Lynparza ) added to standard-of-care Bevacizumab versus Bevacizumab alone in women with or without BRCA-gene mutations.
The trial met its primary endpoint in the intent-to-treat ( ITT ) population with a statistically-significant and clinically-meaningful improvement in progression-free survival ( PFS ) for women taking Olaparib plus Bevacizumab, versus those taking Bevacizumab alone, as a first-line maintenance treatment following response to standard first-line platinum-based chemotherapy and Bevacizumab.
The safety and tolerability profiles observed in PAOLA-1 were generally consistent with those known for each medicine. PAOLA-1 is the second positive phase 3 trial with Olaparib in first-line advanced ovarian cancer.
PAOLA-1 is a randomized, double-blind trial evaluating the efficacy and safety of Olaparib when added to standard-of-care Bevacizumab versus Bevacizumab alone, as first-line maintenance treatment for advanced FIGO stage IIIB-IV high grade serous or endometroid ovarian, fallopian tube, or peritoneal cancer patients who had a complete or partial response to first-line treatment with Platinum-based chemotherapy and Bevacizumab.
Olaparib is a first-in-class PARP inhibitor and the first targeted treatment to block DNA damage response ( DDR ) in cells / tumours harbouring a deficiency in homologous recombination repair, such as mutations in BRCA1 and/or BRCA2.
Inhibition of PARP with Olaparib leads to the trapping of PARP bound to DNA single-strand breaks, stalling of replication forks, their collapse and the generation of DNA double-strand breaks and cancer cell death.
Ovarian cancer is the eighth most common cause of death from cancer in women worldwide. In 2018, there were nearly 300,000 new cases diagnosed and around 185,000 deaths.
Most women are diagnosed with advanced ( stage III or IV ) ovarian cancer and have a five-year survival rate of approximately 30%.
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. ( Xagena )
Source: AstraZeneca & MSD, 2019