Adverse effects associated with treatment with olaparib that led to dose reductions and interruptions did not impact survival benefit for patients with platinum-sensitive ovarian cancer.
Patients with platinum-sensitive recurrent ovarian cancer who experienced adverse effects (AEs) during the first 12 weeks of treatment with olaparib (Lynparza) that led to dose reductions or interruptions did not experience a negative impact on survival, according to a study published in Annals of Oncology.
The median progression-free survival (PFS) was 14.2 months for patients with a 12-week relative dose intensity (RDI) of more than 98%, 19.3 months for an RDI of less than 90% to 98%, and 34.4 months for less than 90% (P = .37). The median overall survival (OS) for an RDI of more than 98% was 49.7 months, 49.5 months for less than 90% to 98%, and 54.1 months for less than 90% (P = .84).
After completing chemotherapy, patients were randomized to receive maintenance olaparib (n = 196) or placebo (n = 99). Among those who received olaparib, 185 patients did not have disease progression during the first 12 weeks of treatment and were included in the analysis. Within this group, 111 patients were included in the RDI of more than 98% cohort, 29 were in the RDI of less than 90% to 98% cohort, and 45 were in the RDI of 90% or less cohort. The mean 12-week RDI was 91.4%, and the median was 100%.
In those with an RDI of 90% or more, the median RDI was 100%, and those with a median RDI of 90% or less, the median RDI was 76.2%. Within the first 12 weeks, 37% of patients in the analyzed population experienced AEs. Twenty-six patients had at least 1 dose reduction, 53 had a dose interruption, and 5 discontinued treatment.
When investigators analyzed patients at a 24-week landmark analysis, 156 patients had not progressed. Additionally, 80 patients had an RDI of more than 98%, 26 had an RDI of less than 90% to 98%, and 33 had an RDI of 90% or less. Those with an RDI of 90% or less had a median RDI of 79.6%.
During the period where OS was analyzed, 780 AE episodes were reported, 130 of which resulted in dose reductions or interruptions. Reasons for reductions or interruptions included anemia, fatigue, and leukopenia.
Investigators divided patients into 2 equal groups based on RDI at 12 weeks. Those in the lower RDI category (n = 93) had a median RDI of 90.5% and a mean of 82.9.% Those in the upper RDI category (n = 92) had a median and a mean of 100%. There was no difference between PFS and OS between these groups.
Consistent results were observed in the 24-week analysis. The median PFS for those with an RDI of more than 98% was 19.7 months, a median of 16.1 months for those with an RDI of less than 90% to 98%, and 31.1 months for an RDI of 90% or less (P = .60). Investigators reported a median OS of 53.4 months for the RDI of over 98% cohort, 59.6 months for the RDI of less than 90% to 98% cohort, and 51.2 months for the RDI of 90% or less cohort (P = .91).
A univariate analysis showed an increased risk of RDI of 90% or less at 12 weeks for those with characteristics such as body weight of 70 kg or less (OR, 1.86; 95% CI, 0.92-3.76), performance status of 1 (OR, 2.54; 95% CI, 1.11-5.82), and nausea (OR, 3.17; 95% CI, 0.9-11.23). Baseline performance status in the multivariate analysis was the only predictor for RDI of 90% or more.
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. Published online February 24, 2022. doi:10.1016/j.annonc.2022.02.222