CMET-25. PROGRESSION-FREE SURVIVAL (PFS) AND SITE OF FIRST PROGRESSION IN HER2+ METASTATIC BREAST CANCER PATIENTS WITH OR WITHOUT BRAIN METASTASES: A POOLED ANALYSIS OF TUCATINIB PHASE I STUDIES
Bibliographic record
Abstract
Brain metastases (BM) are frequent in HER2+ metastatic breast cancer (MBC) occurring in 50% of patients and are associated with significant neurologic morbidity and mortality. Tucatinib is a highly selective irreversible oral HER2+ tyrosine kinase inhibitor that has shown promising results in HER2+ MBC both in patients with and without BM. Two Phase 1b studies of tucatinib were pooled to compare PFS and sites of relapse in patients with or without BM. 77 patients were analyzed, 50 in the 004 (tucatinib + T-DM1) and 27 in the 005 trials (tucatinib + trastuzumab + capecitabine). Patients were heavily pretreated with a median of 3 prior HER2 therapies. Four cohorts were identified: 46% (35) had systemic metastases only, 17% (13) had previously treated (RT with or without surgery) and stable BM, 19% (15) had previously treated and progressive BM and 17% (13) had asymptomatic untreated BM demonstrated by screening MRI. Median PFS across cohorts was similar and no statistically significant difference in PFS was seen when comparing the non-BM cohort to all BM cohorts. The incidence of progression in brain in patients with baseline BM was 51.2% overall compared to an 8.3% in patients without baseline BM. >50% of patients entered tucatinib studies with baseline BM, either previously treated (stable or progressive) or untreated. Patient cohorts analyzed appear to differ only in the site of disease progression. Patients without BM at baseline progress primarily in body whereas patients with baseline BM primarily mostly progress in the brain. Nonetheless, PFS is comparable across cohorts. Furthermore, patients both with and without BM have durable responses with these combination therapies following multiple lines of prior HER2 targeted therapy. These data support the use of tucatinib in both patients with and without BM in the accruing HER2CLIMB trial.
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.
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 | 0.007 | 0.005 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.004 | 0.010 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".