Maintenance olaparib improves PFS, patient-centred benefits in ovarian cancer patients
Maintenance therapy with olaparib significantly improved progression-free survival (PFS) and patient-centred benefits in patients with germline BRCA-mutated, platinum-sensitive relapsed serous ovarian cancer (gBRCAm PSR SOC) compared with placebo, according to the SOLO* 2 trial presented at the American Society of Clinical Oncology (ASCO) Annual Meeting 2017 held in Chicago, Illinois, US.
In this multicentre phase III trial, 295 patients with gBRCAm PSR SOC were randomized to receive olaparib 300 mg twice daily (n=196) or placebo (n=99) following chemotherapy. [ASCO 2017, abstract 5507]
Maintenance olaparib following chemotherapy led to more than 1-year extension in PFS compared with placebo (median 19.1 vs 5.5 months, hazard ratio [HR] 0.30, 95 percent confidence interval [CI], 0.22–0.41; p<0.0001).
This was supported by significant improvements in the secondary efficacy endpoints of time to first (HR, 0.28; p<0.0001) and time to second (HR, 0.37; p<0.0001) subsequent treatment, with clear differences in favour of olaparib, said Prof Michael Friedlander from the University of New South Wales Clinical School, Prince of Wales Hospital, Randwick, Australia.
“[The] delay in progression should also be associated with a longer duration of ‘good quality of life’ for patients,” said Friedlander, citing the additional patient-centred benefits such as longer time without symptoms of disease or toxicity (TWiST, 13.5 vs 7.21 months, 95 percent CI, 2.95–8.58; p<0.0001) and quality-adjusted PFS (QAPFS; 13.96 vs 7.28 months, 95 percent CI, 4.98–8.54; p<0.0001) in patients receiving olaparib vs placebo.
TWiST takes adverse effects and toxicity into account, while QAPFS combines the two key variables PFS and QoL. These may better evaluate the relationship between treatment-associated adverse effects and the potential gains of improved PFS, said Friedlander.
Furthermore, health-related quality of life (HRQoL) was not detrimentally affected by maintenance olaparib vs placebo (difference, -0.03; 95 percent CI, -2.19 to 2.13; p=0.98).
Mean Trial Outcome Index (TOI) was 75, which translates to a better HRQoL, said Friedlander. “The starting TOI was high, so patients were relatively well … olaparib did not appear to negatively impact on the TOI over 12 months.”
Toxicity and adverse events were also observed, with the most common events being nausea (75.9 percent), fatigue (65.6 percent), vomiting (37.4), and diarrhoea (32.8 percent).
“[During maintenance therapy], toxicity of treatment should be acceptable with limited impact on HRQOL,” said Friedlander. Despite the toxicity associated with olaparib treatment, the additional patient-centred benefits obtained from maintenance olaparib supported the prolongation of PFS, he added.