Olaparib maintenance therapy does not have a significant detrimental effect on health-related quality of life in patients with relapsed ovarian cancer despite treatment-related adverse effects, an Australian-led clinical trial shows.
In addition, patient-reported outcomes further support use of the poly(ADP-ribose) polymerase (PARP) inhibitor.
The findings from the SOLO2 trial, randomising 196 patients to oral olaparib (300 mg twice daily) and 99 to placebo, sought to evaluate the balance between treatment toxicity and survival.
Inclusion criteria included a BRCA1/2 mutation, at least two previous lines of platinum-based chemotherapy with a radiological or CA125 tumour marker response to the most recent regimen, and an ECOG performance status of 0-1.
Mean total duration of treatment was 19.4 months for olaparib and 5.6 months for placebo.
Despite adverse effects including nausea, fatigue and abdominal pain, there was no significant difference from baseline to one year in the Functional Assessment of Cancer Therapy-Ovarian Cancer Trial Outcome Index (FACT-0/TOI) score (75.26 to 72.36 with olaparib v 77.12 to 74.25 with placebo).
Quality-adjusted progression-free survival (QAPFS) was 13.96 months with olaparib compared to 7.28 months with placebo and the mean time without symptoms and treatment toxicity (TWiST) was also longer on olaparib than placebo (15.03 v 7.70 months).
“This study showed that the increase in progression-free survival with maintenance olaparib in SOLO2 is supported by clinically meaningful patient-centred benefits, including significant improvements in both TWiST and QAPFS, which take into consideration the adverse effects of olaparib,” the study said.
Lead author Professor Michael Friedlander, from the University of New South Wales and Prince of Wales Hospital, told the limbic the advantage of maintenance therapy was that patients could remain well for longer and avoid or delay further chemotherapy.
“You cannot make patients who have no cancer-related symptoms after response to chemotherapy feel any better as they are usually pretty well apart from getting over the side effects of the chemotherapy they have just had. So you cannot improve quality of life but you could make it a lot worse if there were a lot of side effects with olaparib.”
He added that measures of quality of life and patient-reported outcomes should be incorporated into future trials of maintenance.
“We also found in a different study – Study 19 – that about 11% of patients remained in remission on maintenance olaparib for over five years after starting treatment which is unprecedented,” he said.
A Comment in Lancet Oncology said that PARP inhibitors allow ovarian cancer to be treated as a chronic disease over a long duration.
“In such settings, quality of life is particularly important in addition to prolonging progression-free survival.”
“For patients in whom a median overall survival of more than 12 months is expected, progression-free survival is recommended to be supported by additional measures of clinical benefit, such as time to second subsequent therapy or death or patient-reported outcomes.”