A phase II study of foretinib in triple-negative, recurrent/metastatic breast cancer: NCIC CTG trial IND.197 (NCT01147484).
Bibliographic record
Abstract
1036 Background: Met, a receptor tyrosine kinase, is preferentially expressed in basal-like compared to luminal breast cancer. In murine models, overexpression of the oncogenic Met receptor transgene induces tumors with human basal gene expression characteristics supporting Met inhibition as a treatment strategy for triple negative (TN) breast cancer. Foretinib is an oral multi-kinase inhibitor of Met, RON, AXL, TIE-2 and VEGF receptors with anti-tumor activity in advanced HCC and papillary renal cell cancer. Methods: Patients (pts) with TN breast cancer and 0-1 prior regimens for metastatic disease received daily foretinib 60 mg po in a 2-stage single arm trial. Primary endpoints were objective response and early progression rates per RECIST 1.1. Tumor samples were centrally reviewed to confirm ER/PR/HER2 status and for correlative studies including Met, PTEN and EGFR expression. Stage 1 accrual required 23 response-evaluable Met unselected patients with accrual continuing if >/= 1 response or < 17 early progressions (PD <= 8 weeks on study) were observed. Results: Accrual is 29 pts to date; 24 are eligible, 22 evaluable for toxicity and 15 for response. Median age is 56 y (43-81), ECOG PS 0-1 in 23/24. Grade 3 laboratory adverse events were: lymphopenia (9%), elevations in ALT (5%), GGT (5%) and INR (5%). Treatment-related non-hematologic toxicities included (all/grade 3-4) fatigue (64%/5%), nausea (55%/5%), diarrhea (41%/5%), hypertension (32%/14%), vomiting (27%/0%), anorexia (23%/5%) and rash (14%/0%). Three SAEs possibly related to foretinib included; asymptomatic pulmonary embolism, reversible CHF and pleural effusion with QTc prolongation. One PR (7%), 8 early PD (53%) and 6 SD (40%) have been observed to date with median SD duration of 5.4 months (range 2.7-5.5). Preliminary correlative results (IHC): 5/8 (62.5%) evaluable Met positive cases had SD and 4/5 (80%) Met negative cases had PD as best response. Met IHC was negative in the pt with PR. Conclusions: Foretinib shows preliminary evidence of activity and tolerability in metastatic, TN breast cancer. Stage 2 of accrual will include 15 pts with pre-treatment biopsies of metastases and circulating tumor cell collection.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.011 | 0.002 |
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".