Abstract P6-16-02: Beta-adrenergic receptor blockers (BB) and increased progression free survival (PFS) in patients with advanced triple negative breast cancer (TNBC): A retrospective analysis of the ROSE/TRIO012 study
Bibliographic record
Abstract
Abstract Introduction: Recent retrospective studies suggest beta-adrenergic blocking drugs are associated with improved survival in patients with a wide range of cancers. Although limited and discordant data suggest that the use of BB may increase overall survival (OS) of patients with localized breast cancer (BC), there is no information on the effects of BB in women with advanced BC, which may be a more appropriate clinical scenario to evaluate anti-cancer effects of new treatment strategies. We analyzed the relationship between BB use and clinical outcomes in the ROSE/TRIO012 study, a double-blinded multinational registration phase III trial that randomized 1,144 patients with HER2-negative advanced BC to receive first-line docetaxel in combination with ramucirumab (RAM) or placebo. Objective: To explore the association between BB use and BC outcomes in patients participating in the ROSE/TRIO-012 trial. Methodology: We retrospectively compared PFS,OS,Overall Response Rate (ORR) and Clinical Benefit Rate (CBR) using the ITT population, in patients who received BB during the trial with those who did not receive them. PFS and OS were estimated using the Kaplan-Meier method. PFS and OS of both treatment groups were compared using the Log-Rank test. Cox proportional models were fitted to determine the association between BB, PFS and OS. ORR and CBR in both groups were compared using the Fisher's Exact Test. Results: 153/1,144 (13%) patients received BB during the trial. Median PFS in patients treated with BB was 10.3 months, compared to 8.3 months in patients who did not receive them (HR 0.81; 95% CI 0.66-0.99; p=0.0379). In patients treated with BB only after enrolment (57/153, 37%) median PFS was 15.5 months vs. 8.3 months in patients with no BB (p=0.0005). In the subset of patients with TNBC, median PFS was 13 months if received BB compared to 5.2 months if no BB (HR 0.52; 95% CI 0.34-0.79; p=0.002). No difference in PFS was observed in patients with hormone receptor positive BC. The magnitude of PFS benefit in the RAM arm was similar as the whole ITT population (HR 0.73; 95% CI 0.57-0.94; p=0.014. If BB received only after enrolment HR 0.50; 95% CI 0.35-0.72; p=0.0003). The benefit of BB intake in PFS was independent of development of treatment-emergent hypertension (hypertension occurring within 42 days of first study drug administration; HR 0.92; 95% CI 0.73-1.15; p=0.476) but dependent on treatment arm (HR 0.86; 95% CI 0.74-0.99; p=0.037). The test for interactions between BB and treatment arm was not significant (p =0.276). No differences in OS, ORR or CBR were seen. Conclusions: In this exploratory post-hoc analysis of the ROSE/TRIO012 study, BB intake was associated with a significant improvement in PFS compared to patients who did not receive them, particularly in patients with TNBC and patients not previously exposed to these drugs. Further evaluation of the BB intake on BC outcomes warrants evaluation in a prospectively-designed clinical trial. Citation Format: Spera G, Fresco R, Fung H, Dyck JRB, Pituskin E, Patterson I, Aspeslet L, Mackey JR. Beta-adrenergic receptor blockers (BB) and increased progression free survival (PFS) in patients with advanced triple negative breast cancer (TNBC): A retrospective analysis of the ROSE/TRIO012 study [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-16-02.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.003 | 0.004 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".