SYST-05 OPTIMIZING HER2-TARGETED THERAPIES (TT) FOR BREAST CANCER (BC) LEPTOMENINGEAL METASTASES (LM): A SYSTEMATIC REVIEW AND META-ANALYSIS
Bibliographic record
Abstract
Abstract INTRODUCTION LM is a debilitating condition associated with metastatic cancers, including BC. When oncogenic drivers are identified, TT represents an appealing therapeutic strategy. However, the efficacy of TT for LM is unknown as LM patients are routinely omitted from clinical trials. METHODS We conducted a systematic review and meta-analysis of individual patient data to evaluate the effectiveness of HER2-TT in HER2+ BCLM in accordance with PRISMA guidelines. TTs evaluated included trastuzumab (intrathecal (IT) or intravenous (IV)), trastuzumab-emtansine, trastuzumab-deruxtecan, and lapatinib. Primary outcome was overall survival (OS). RESULTS Of 7780 abstracts screened, 91 publications and a total of 109 patients were included in the final analysis. Patients receiving chemotherapy (either IT, IV, or as part of an antibody-drug conjugate) concurrently with HER2-TT (N=57) exhibited a median OS (mOS) of 44.0 months, compared to patients treated with targeted anti-HER2 therapies alone (N=52), which exhibited a mOS of 14.5 months (P=0.009, hazard ratio (HR): 0.538, 95% confidence interval (CI): 0.328-0.883). Patients receiving IT trastuzumab (N=83) exhibited a median progression-free survival (mPFS) and mOS of 6.0 and 21.0 months, respectively, while patients receiving IV trastuzumab (N=14) exhibited a mPFS and mOS of 6.5 and 27.0 months, respectively (PFS: P=0.31, HR: 0.712, 95% CI: 0.331-1.531; OS: P=0.68, HR: 1.154, 95% CI: 0.587-2.266). In the subgroup of patients receiving IT trastuzumab (N=58), those who concurrently received IT chemotherapy (N=48) exhibited mPFS and mOS of 5.7 and 14.0 months, respectively, while patients concurrently receiving IV chemotherapy (N=10) exhibited a mPFS and mOS of 6.0 and 27.0 months, respectively (PFS: P=0.45, HR: 1.360, 95% CI: 0.602-3.073; OS P=0.29, HR: 1.821, 95% CI: 0.630-5.260). CONCLUSIONS HER2-TT is an effective therapeutic strategy for BCLM. Patients with BCLM receiving concurrent cytotoxic chemotherapy alongside HER2-TT experience prolonged mOS. IV and IT trastuzumab are similarly effective. Univariate and multivariate analyses will be presented.
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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 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.016 | 0.004 |
| Bibliometrics | 0.001 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.005 | 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".