Olaparib Dose Reduction and Interruption Show No Impact on Survival in Patients With BRCA-Mutated Ovarian Cancer

Olaparib dose reduction and interruption for the management of olaparib-associated adverse events (AEs) in patients with ovarian cancer during the first 12 weeks resulted in no impact on progression-free survival (PFS) and overall survival (OS), according to study findings.

“Olaparib maintenance therapy is now the standard of care in patients with BRCA-mutated ovarian cancer,” wrote Katherine Francis, MBBS, MMed, National Health and Medical Research Council Clinical Trials Centre, The University of Sydney, Australia, and colleagues.

The study analyzed data from SOLO2 double-blind, randomized, placebo-controlled phase 3 clinical trial to assess the impact of olaparib dose reduction and interruption on PFS and OS in patients BRCA-mutated, platinum-sensitive recurrent ovarian cancer. 

“Maintenance treatment is often administered for prolonged periods of time to these well patients, and hence tolerability is important minimise the impact on patient quality of life,” Dr Francis and colleagues explained.

In the trial, AE-associated olaparib interruption, dose reduction, and discontinuation occurred in 50%, 28%, and 17% of patients, respectively. The study compared relative dose intensity (RDI) during the first 12 weeks of patient treatment, with patients classified as either RDI >98%, RDI 90% to 98%, or RDI <90% and utilized Cox regression analysis to analyze categories for PFS and OS using a 12-week landmark. Baseline factors were correlated with RDI at 12 weeks using logistic regression analysis.

The study calculated the mean 12-week RDI for patients on olaparib (n = 185) at 91.4%.  In patients with 12-week RDI >98% (n = 110), PFS was 14.2 months and OS was 49.7 months. In patients with 12-week RDI 90% to 98% (n = 29) PFS and OS were 29.3 and 49.5 months, respectively. PFS in Patients with 12-week RDI <90% (n = 45) was 34.4 months and OS was 54.1 months.

Baseline performance status 1 (odds ratio [OR], 2.54; 95% confidence interval [CI], 1.11 to 5.82), nausea (OR, 3.17; 95% CI, 0.9 to 11.23), and body weight ≤70 kg (OR, 1.86; 95% CI, 0.92 to 3.76) increased risk of RDI ≤90%, according to the study.

“Dose reduction and interruption for the management of olaparib-associated AEs during the first 12 weeks did not impact on PFS and OS,” concluded Dr Francis et al. “When counselling patients who require dose reductions or interruptions due to AEs, the results of this study will help to assure patients that their outcomes will not be adversely affected.”

Source:                                        

Francis KE, Kim SI, Friedlander M, et al. The impact of olaparib dose reduction and treatment interruption on treatment outcome in the SOLO2/ENGOT-ov21 platinum-sensitive recurrent ovarian cancer. Ann Oncol. 2022;33(6):593-601. doi:10.1016/j.annonc.2022.02.222