Comparison of real-world outcomes over time in a large population-based cohort of patients with metastatic breast cancer.
Bibliographic record
Abstract
e13112 Background: The treatment of metastatic breast cancer (MBC) has evolved over the past two decades, with a number of new therapeutics being introduced. Real-world evidence is needed to evaluate whether these new therapeutics have made an impact on population survival, as improvements in survival seen within clinical trials do not necessarily translate into the real world. The purpose of this study was to investigate whether survival for each subtype of MBC has improved in patients diagnosed with MBC between 2003 and 2017. In addition, for the HER2+ subtype, we aimed to characterize and correlate changes in the use of anti-HER2 therapeutics with any observed real-world survival changes. Methods: The study included residents of British Columbia, Canada who were diagnosed with de novo or recurrent MBC during one of the following four time periods: 2003 to 2005, 2007 to 2009, 2011 to 2013, and 2014 to 2017. Patients were included whether or not they received any systemic therapies for MBC. Patient, disease, and treatment characteristics were obtained through medical records and the Breast Cancer Outcomes Unit database. Survival estimates were calculated using the Kaplan-Meier method. Univariable analyses were performed using the log-rank test, and multivariable analyses (MVA) were performed using the Cox proportional hazards model. Results: 5,924 patients were diagnosed with MBC during one of the four time periods. 3,756 (63%) had hormone receptor positive (HR+) subtype, 1,145 (19%) had HER2+ subtype, 770 (13%) had triple negative (TN) subtype, and 253 (4%) had unknown subtype. For the HR+ subtype, overall survival (OS) was similar for cohorts 1 to 3 (median survivals: 751 days, 704 days, and 702 days). However, OS was longer for cohort 4 (median survival: 855 days) compared to cohort 3 ( p < 0.001). For the HER2+ subtype, OS was similar for cohorts 1 to 3 (median survivals: 594 days, 511 days, and 592 days). However, OS was longer for cohort 4 (median survival: 791 days) compared to cohort 3 ( p = 0.03). For the TN subtype, there was no significant change in OS for the four cohorts (median survivals: 234 days, 236 days, 274 days, and 255 days). On MVA, younger age, non-TN subtype, time cohort 4, de novo presentation, and disease-free interval of > 12 months were associated with improved OS. For the HER2+ subtype, a greater percentage of patients in the later cohorts were treated with pertuzumab ( p < 0.001) and trastuzumab emtansine (T-DM1) ( p < 0.001), with 12.4% and 36.3% respectively receiving these drugs in cohort 3 compared to 80.9% and 52.5% respectively in cohort 4. Conclusions: Patients diagnosed with MBC of the HR+ or HER2+ subtypes in the 2014 to 2017 time period had improved real-world outcomes compared to those diagnosed in earlier time periods. Improvements in real-world outcomes were likely associated with new therapeutic agents with demonstrated OS benefit in trial settings.
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How this classification was reachedexpand
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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, 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".