Mark E. Robson, MD
Improvements in progression-free survival (PFS) with olaparib (Lynparza) over treatment of physician's choice (TPC) remained consistent regardless of baseline tumor burden for patients with HER2-negative breast cancer with a germline BRCA
1/2 mutation (gBRCA
1/2m), according to an exploratory analysis from the phase III OlympiAD trial presented at the 2018 Miami Breast Cancer Conference (MBCC).
Although not powered to show statistical significance between the groups, in those with one metastatic site (n = 71) the median PFS with olaparib was 8.4 months compared with 4.2 months with TPC (HR, 0.62; 95% CI, 0.35-1.13). In patients with ≥2 metastatic sites (n = 231), the median PFS was 6.5 months with olaparib compared with 3.0 months for TPC, which crossed the barrier for statistical significance (HR, 0.59; 95% CI, 0.43-0.82).
Across the full OlympiAD trial (n = 302), the median PFS was 7.0 months with olaparib and 4.2 months for TPC (HR, 0.58; 95% CI, 0.43-0.80; P
<.001). Additionally, olaparib monotherapy also showed significant benefit for key secondary endpoints, including improvements in health-related quality of life (HRQoL). Based on these findings, in January 2018 the FDA approved olaparib as a treatment for patients with HER2-negative, gBRCA
1/2m metastatic breast cancer following prior chemotherapy.
“This study [at MBCC] confirms and deepens our understanding of the relative benefits of olaparib compared to chemo, and affirms the significance of this new option for the treatment of some women with advanced breast cancer,” lead investigator and lead author of the MBCC analysis Mark E. Robson, MD, chief, Breast Medicine Service, Memorial Sloan Kettering Cancer Center, told OncLive
The OlympiAD trial randomized 302 patients with HER2-negative, gBRCA
1/2m metastatic breast cancer to receive 300-mg olaparib tablets twice daily (n = 205) or TPC (n = 97). Approximately 71% of patients had received prior chemotherapy in the metastatic setting, and 28% had received prior platinum-based therapy in the neoadjuvant, adjuvant, or metastatic setting. At baseline, HRQoL by the EORTC QLQ-C30 questionnaire was similar between groups.
Overall, olaparib double objective response rate (ORR) compared with TPC (59.9% vs 28.8%). A complete response was obtained for 9% of those in the olaparib group versus 1.5% for TPC. The median best percentage change from baseline in target lesion size for patients treated with olaparib was -45.1% (range, -100% to +77%) compared with -14.8% in the TPC group (range, -100% to +89%).
More than half of patients had responded to treatment by the time of the first visit, with a median time to response of 47 days with olaparib and 45 days for TPC. ORR at the 6-week follow-up was 32.4% with olaparib and 16.7% with TPC. ORR for the full study was confirmed in a post-hoc assessment, which validated initial responses with repeat imaging at ≥4 weeks. In this analysis, the confirmed ORR was 52.1% with olaparib and 22.7% for TPC. Treatment duration was ≥6 months for 60.0% of patients in the olaparib arm compared with 27.5% in the TPC group.
Median time to first subsequent therapy (TFST) and median time to second subsequent therapy (TSST) were longer with olaparib versus TPC. The median TFST was 9.4 versus 4.2 months for olaparib and TPC, respectively, (HR, 0.34; 95% CI, 0.24-0.47; P
<.0001). The median TSST was 14.3 months for olaparib versus 10.5 months for TPC (HR, 0.53; 95% CI, 0.38-0.74; P
There were fewer grade ≥3 adverse events (AEs) with olaparib compared with TPC. In the olaparib arm, 36.6% of patients had a grade ≥3 AE compared with 50.5% with TPC. Additionally, there were fewer AE-related discontinuations in the olaparib arm versus TPC (4.9% vs 7.7%)
A mean 7.5-point improvement in HRQoL with was experienced by patients treated with olaparib versus TPC (95% CI, 2.48-12.44; P
= .0035). The HRQoL score increased by 3.9 points (±1.2) with olaparib and decreased by -3.6 points (±2.2) in the TPC group. More patients experienced a clinically meaningful improvement (≥10-point increase) in HRQoL in the olaparib arm compared with TPC (38.8% vs 22.8%; odds ratio, 2.15; 95% CI, 1.10-4.42).
Fewer patients in the olaparib arm experienced a deterioration in their HRQoL over the course of the study, with a 56% reduction in the risk of deterioration with the PARP inhibitor (HR, 0.44; 95% CI, 0.25-0.77; P
= .004). The median time to HRQoL deterioration was 15.3 months for TPC and was not calculable in the olaparib arm. At 6 months, 81.5% of patients in the olaparib group were deterioration-free compared with 61.2% in the TPC arm. At 12 months, the deterioration-free rates were 64.0% and 53.5%, respectively.
Robson ME, Domchek SM, Tung N, et al. Further efficacy and health-related quality-of-life outcomes for olaparib monotherapy versus standard single-agent chemotherapy treatment of physician's choice (TPC) in patients with HER2-negative metastatic breast cancer and a germline BRCA mutation. Presented at: 35th Miami Breast Cancer Conference, March 8-11, 2018, Miami Beach, Florida. Abstract 619.