Safety and efficacy of veliparib plus carboplatin/paclitaxel in patients with HER2-negative metastatic or locally advanced breast cancer: subgroup analyses by germline <i>BRCA1</i> / <i>2</i> mutations and hormone receptor status from the phase-3 BROCADE3 trial
Why this work is in the frame
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Bibliographic record
Abstract
Purpose: To evaluate efficacy and safety of veliparib combined with carboplatin/paclitaxel in patients with advanced human epidermal growth factor receptor 2 (HER2)-negative, germline BRCA (g BRCA)-associated breast cancer defined by hormone receptor (HR) and g BRCA1/ 2 mutation status. Patients and Methods: In this phase-3, double-blind, placebo-controlled trial, patients ( N = 509) with advanced HER2-negative breast cancer and g BRCA1/2 mutations were randomized 2:1 to receive veliparib plus carboplatin/paclitaxel or placebo plus carboplatin/paclitaxel. Patients who discontinued chemotherapy prior to disease progression continued receiving blinded veliparib/placebo monotherapy. The primary endpoint was investigator-assessed progression-free survival (PFS). Subgroup analyses of PFS stratified by HR and g BRCA1/2 mutation status were prespecified. Results: In the intention-to-treat population, there were similar proportions of patients with g BRCA1 versus g BRCA2 mutations (51% vs 49%) and HR+ disease versus triple-negative breast cancer (TNBC) (52% vs 48%). Median PFS was longer in the veliparib arm compared with the placebo arm for all subgroups (HR+: 13.0 vs 12.5 months, hazard ratio (95% confidence interval (CI)): 0.69 (0.52, 0.93), p = 0.013; TNBC: 16.6 vs 14.1 months, hazard ratio (95% CI): 0.72 (0.52, 1.00), p = 0.052; g BRCA1: 14.2 vs 12.6 months, hazard ratio (95% CI): 0.75 (0.55, 1.03), p = 0.073; g BRCA2: 14.6 vs 12.6 months, hazard ratio (95% CI): 0.69 (0.50, 0.95); p = 0.021). Benefit was durable, with improved PFS rates at 2 years (HR+, 27.5% vs 15.3%; TNBC, 40.4% vs 25.0%) and 3 years (HR+, 17.5% vs 8.6%; TNBC, 35.3% vs 13.0%) in all subgroups. g BRCA status ( BRCA1 vs BRCA2) did not substantially affect the carboplatin/paclitaxel ± veliparib toxicity profile. Conclusion: Veliparib plus carboplatin/paclitaxel resulted in durable benefit in subgroups defined by HR status or by g BRCA1 versus g BRCA2 mutation. Overall, addition of veliparib to carboplatin/paclitaxel was tolerable, and there were no clinically meaningful differences in adverse events between the g BRCA1 versus g BRCA2 and HR+ versus TNBC subgroups. Trial Registration: NCT02163694, https://clinicaltrials.gov/ct2/show/NCT02163694
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it