The impact of olaparib dose reduction and treatment interruption on treatment outcome in the SOLO2/ENGOT-ov21 platinum-sensitive recurrent ovarian cancer

Abstract

Background Maintenance treatment with poly (ADP-ribose) polymerase (PARP) inhibitor is now the standard of care in patients with BRCA mutated platinum-sensitive recurrent ovarian cancer following response to chemotherapy. In the SOLO2 trial, adverse event (AE) associated olaparib interruption, dose reduction, and discontinuation occurred in 50%, 28%, and 17% of patients, respectively. We used data from SOLO2 trial to evaluate the impact of dose alterations on survival outcomes and identified baseline characteristics associated with dose alteration. Patients and methods We computed relative dose intensity (RDI) defined as received dose as a percentage of the standard dose (300mg twice a day) during the first twelve weeks on treatment. Patients were categorized into RDI >98%, RDI 90-98% and RDI < 90%. The association between RDI categories with progression-free survival (PFS) and overall survival (OS) were examined using a 12-week landmark Cox regression analysis. Logistic regression analysis was used to correlate baseline factors with RDI at 12-weeks. Results In patients on olaparib included in the landmark analysis (n = 185) the mean 12-week RDI was 91.4%. There was no significant difference across 12-week RDI >98% (n = 110), 90-98% (n = 29), and <90% (n = 45) categories for PFS (median, 14.2 vs. 19.3 vs. 34.4 months; P=.37) and OS (median, 49.7 vs. 49.5 vs. 54.1 months; P=.84). Risk of RDI ≤90% increased with baseline performance status 1 (OR: 2.54; 95% CI: 1.11-5.82) any nausea (OR: 3.17; 95% CI: 0.9-11.23) and with body weight ≤ 70kg (OR: 1.86; 95% CI: 0.92-3.76). Conclusions Dose reduction and interruption for the management of olaparib associated AE during the first 12 weeks did not impact on PFS and OS. When counselling patients requiring dose reductions or interruptions due to AEs, the results of this study will help assure patients that their outcomes will not be adversely affected.