Despite toxicity, olaparib maintenance therapy is associated with improved patient-reported symptoms outcomes and improved quality-adjusted progression-free survival (PFS) among patients with germline BRCA mutation-positive, platinum-sensitive relapsed serious ovarian cancer, according to results of the phase III SOLO2 clinical trial presented (abstract 5507) at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting, held June 2–6 in Chicago.
“There was no significant detrimental effect of olaparib versus placebo on health-related quality of life (HRQOL),” reported lead study author Michael Friedlander, MD, of the University of New South Wales, Prince of Wales Hospital, in Randiwick, Australia. “Despite the toxicity associated with olaparib versus placebo, significant patient-centered benefits of olaparib were observed, including significantly longer quality-adjusted progression-free survival and significantly longer time without symptoms of disease or treatment toxicity.”
Olaparib is a PARP inhibitor that targets poly-ADP ribose polymerase, a DNA repair enzyme.
The study authors sought to test the hypothesis that olaparib maintenance therapy would not harm HRQOL compared to placebo “and would be associated with additional patient-centered benefits to support the prolongation of PFS, the primary endpoint of SOLO2,” Friedlander said. SOLO2 findings were previously reported to include significant PFS benefits for olaparib tablet maintenance therapy (hazard ratio [HR], 0.30; 95% CI: 0.22–0.41; P < .0001), Friedlander noted.
“But this benefit comes at a cost and that cost is toxicity,” Friedlander said.
To determine if treatment toxicity impacts HRQOL, the research team analyzed change from baseline in Trial Outcome Index (TOI, based on FACT-O questionnaire responses) and the EQ-5D-5L questionnaire, measures of ovarian cancer symptoms, and functional and physical well-being. Questionnaires were administered at baseline, day 29, alongside RECIST assessments every 12 weeks until tumor progression, and upon study discontinuation.
Patients were “relatively well” at baseline, when they started maintenance therapy, with an average TOI score of 75, and olaparib “did not negatively impact” TOI over 12 months, Friedlander said. The adjusted decline in TOI over 12 months from baseline was -2.90 for patients receiving olaparib and -2.87 for patients in the placebo group (P = .98), he said.
Quality-adjusted PFS was significantly longer among patients receiving olaparib than placebo (13.96 vs 7.38 months; P < .0001). Similarly, olaparib was associated with improved time without symptoms of disease or toxicity (TWiST), a measure of “good quality of life” time during which patients are free of symptomatic disease and adverse events (TWiST: 13.5 vs 7.21 months; P < .0001).