SOLO-1 trial: Olaparib maintenance therapy cut risk of disease progression or death by 70% in patients with newly-diagnosed, advanced BRCA-mutated ovarian cancer
The results from the phase III SOLO-1 trial testing Olaparib ( Lynparza ) tablets as a maintenance treatment for patients with newly-diagnosed, advanced BRCA-mutated ( BRCAm ) ovarian cancer who were in complete or partial response following 1st-line standard Platinum-based chemotherapy, were announced.
Results of the trial have confirmed the statistically-significant and clinically-meaningful improvement in progression-free survival ( PFS ) for Olaparib compared to placebo, reducing the risk of disease progression or death by 70% ( hazard ratio, HR 0.30 [ 95% CI 0.23-0.41 ], p less than 0.001 ).
At 41 months of follow-up, the median PFS for patients treated with Olaparib was not reached compared to 13.8 months for patients treated with placebo. Of those receiving Olaparib, 60% remained progression-free at 36 months compared to 27% of women in the placebo arm.
Women with ovarian cancer are often diagnosed with advanced disease, which is associated with poor long-term survival rates.
The SOLO-1 results have demonstrated the potential of Olaparib maintenance therapy earlier in the treatment pathway and reinforce the importance of identifying a patient’s BRCA mutation status at the time of diagnosis.
The SOLO-1 safety profile was in line with that observed in prior clinical trials. The most common adverse events greater than or equal to 20% were nausea ( 77% ), fatigue / asthenia ( 63% ), vomiting ( 40% ), anaemia ( 39% ) and diarrhoea ( 34% ).
The most common greater than or equal to grade 3 adverse effects were anaemia ( 22% ) and neutropenia ( 9% ).
Seventy-two percent of patients on Olaparib remained on the recommended starting dose.
Additionally, 88% of patients on Olaparib continued treatment without an adverse effects-related discontinuation.
SOLO-1 is a phase III randomised, double-blinded, placebo-controlled, multicentre trial to evaluate the efficacy and safety of Olaparib tablets ( 300 mg twice daily ) as maintenance monotherapy compared with placebo, in newly-diagnosed patients with advanced BRCAm ovarian cancer following Platinum-based chemotherapy.
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.
Patients were randomised ( 2:1 ) to receive Olaparib or placebo for up to two years or until disease progression ( at the investigator’s discretion ).
The primary endpoint was progression-free survival and key secondary endpoints included time to second disease progression or death, time to first subsequent treatment and overall survival.
Olaparib is a 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.
Ovarian cancer is a leading cause of cancer death in women worldwide, with a five-year survival rate of 19%.
In 2018, there were over 295,000 new cases diagnosed and around 184,799 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. ( Xagena )
Source: European Society for Medical Oncology - ESMO Congress, 2018