Olaparib Maintenance ‘Substantial Benefit’ For Advanced BRCA-Positive Ovarian Cancer

Patients with a new diagnosis of advanced ovarian cancer who have a BRCA1 or BRCA2 mutation derive a significant progression-free survival benefit from maintenance PARP inhibitor therapy

medwireNews: SOLO1 trial results suggest that advanced ovarian cancer patients with a BRCA mutation may have a 70% reduction in the risk of disease progression or death if given maintenance PARP inhibitor treatment. 

The phase III trial included 391 patients with a new diagnosis of International Federation of Gynecology and Obstetrics stage III or IV high-grade serous or endometrioid ovarian cancer, primary peritoneal cancer and/or fallopian tube cancer. All patients had BRCA1 and/or BRCA2 germline mutations except for two participants with a somatic mutation.  

After achieving a partial or complete response to platinum-based chemotherapy, the patients were randomly assigned to receive olaparib 300 mg twice daily for at least 2 years or placebo, and followed up for a median of 41 months. 

The Kaplan–Meier estimate of 1-year progression-free survival (PFS) was 88% with olaparib versus 51% for placebo and 74% versus 35% at 2 years. And the corresponding rates at 3 years and 4 years were 60% versus 27%, and 53% versus 11%. 

This gave a significant 3-year hazard ratio for progression or death of 0.30, reported presenting author Kathleen Moore, from the University of Oklahoma in Oklahoma City, USA, at the ESMO 2018 Congress in Munich, Germany. 

Writing in a simultaneously published article in The New England Journal of Medicine, the investigators emphasize that there was “no evidence of a change in the shape of the Kaplan-Meier curve for olaparib after 24 months, when patients with no evidence of disease stopped the intervention, in accordance with the protocol.” 

“[T]his finding indicates a sustained benefit of olaparib beyond the completion of treatment”, they say. 

Furthermore, the endpoint of second PFS was also significantly longer with olaparib compared with placebo, comment Kathleen Moore et al, which suggests that “olaparib did not diminish patients’ ability to benefit from subsequent therapy”. 

They add: “Data on overall survival are currently immature but show no evidence that olaparib had a detrimental effect on survival.” 

Safety analysis was consistent with earlier studies of olaparib, with grade 3 or 4 events occurring in 39% of patients given the PARP inhibitor and 18% of controls. 

“Adverse events were usually managed by dose interruption or dose reduction, rather than discontinuation,” the SOLO1 investigators note, with nausea and anaemia the most common reasons given for stopping treatment. 



Moore K, Colombo N, Scambia G, et al. Maintenance olaparib in patients with newly diagnosed advanced ovarian cancer . N Engl J Med; Advance online publication 21 October 2018.
DOI: 10.1056/NEJMoa1810858  

Moore K, Colombo N, Scambia G, et al. Maintenance olaparib following platinum-based chemotherapy in newly diagnosed patients (pts) with advanced ovarian cancer (OC) and a BRCA1/2 mutation (BRCAm): Phase III SOLO1 trial . ESMO 2018 Congress, 19-23 October, Munich, Germany (LBA7_PR).

Watch the ESMO Video Highlight interview on this study

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