Olaparib efficacy in patients with germline BRCA-mutated, HER2-negative metastatic breast cancer: subgroup analyses from the phase III OlympiAD trial.
Elżbieta SenkusSuzette DelalogeSusan M DomchekPierfranco ConteSeock-Ah ImBinghe XuAnne ArmstrongNorikazu MasudaAnitra FieldingMark RobsonNadine TungPublished in: International journal of cancer (2023)
In the primary analysis of the phase III OlympiAD trial, olaparib significantly prolonged progression-free survival (PFS) versus chemotherapy treatment of physician's choice (TPC) in patients with germline BRCA-mutated (gBRCAm), HER2-negative metastatic breast cancer (mBC). We report subgroup analyses for the final analysis at a median OS follow-up of 18.9 months (olaparib) and 15.5 months (TPC). Patients (N=302) with gBRCAm, HER2-negative mBC and ≤2 previous lines of chemotherapy for mBC were randomized 2:1 to open-label olaparib (300mg twice daily) or TPC. All subgroup analyses were prespecified except site of metastases. Investigator-assessed median PFS was 8.0 months (95% confidence interval [CI] 5.8-8.4; 176/205 events) for olaparib and 3.8 months (95% CI 2.8-4.2; 83/97 events) for TPC (hazard ratio 0.51, 95% CI 0.39-0.66). In subgroup analyses, median PFS hazard ratios (95% CI) favoured olaparib: hormone receptor status (triple-negative: 0.47, 0.32-0.69; hormone receptor-positive: 0.52, 0.36-0.75); gBRCAm (BRCA1: 0.49, 0.35-0.71; BRCA2: 0.49, 0.33-0.74); site of metastases (visceral/CNS: 0.53, 0.40-0.71; non-visceral: 0.45, 0.23-0.98); prior chemotherapy for mBC (yes: 0.51, 0.38-0.70; no: 0.49, 0.30-0.82); prior platinum-based chemotherapy for BC (yes: 0.49, 0.30-0.83; no: 0.50, 0.37-0.69); progressive disease at randomization (yes: 0.48, 0.35-0.65; no: 0.61, 0.36-1.07). Investigator-assessed objective response rates were higher across all subgroups with olaparib (35-68%) versus TPC (5-40%). Global health status/health-related quality of life increased in all subgroups with olaparib versus decreased/no change with TPC. These data confirm the consistency of olaparib benefit across patient subgroups in OlympiAD. This article is protected by copyright. All rights reserved.
Keyphrases
- phase iii
- open label
- clinical trial
- phase ii
- metastatic breast cancer
- double blind
- placebo controlled
- phase ii study
- free survival
- study protocol
- locally advanced
- multiple sclerosis
- physical activity
- breast cancer risk
- emergency department
- newly diagnosed
- type diabetes
- prognostic factors
- ejection fraction
- big data
- dna repair
- decision making
- squamous cell carcinoma
- randomized controlled trial
- rectal cancer
- machine learning
- smoking cessation