A phase 2 study of napabucasin with weekly paclitaxel in previously treated metastatic breast cancer.
Bibliographic record
Abstract
1084 Background: Napabucasin is a first-in-class cancer stemness inhibitor, identified by its ability to inhibit STAT3-driven gene transcription and spherogenesis of cancer stem cells (Li et al PNAS 112 (6):1839, 2015). Napabucasin has shown potent synergistic preclinical anti-tumor activity with paclitaxel (PTX). In a phase Ib dose escalation study in patients (pts) with advanced solid tumors, Napabucasin plus weekly paclitaxel was well tolerated. A phase II expansion cohort was opened for pts with previously treated metastatic breast cancer (MBC). Methods: Pts with metastatic MBC for whom weekly PTX was a reasonable treatment option received Napabucasin 240, 480, or 500 mg orally, twice daily in combination with paclitaxel 80 mg/m2 IV weekly on 3 of every 4 weeks. Adverse events were evaluated using CTCAE v4.03 and objective tumor assessments were obtained every 8 weeks per RECIST 1.1 criteria. Results: A total of 50 pts were enrolled including 34 with triple-negative disease (negative for estrogen receptor [ER], progesterone receptor [PR], and Her2 and no prior history of positive receptor status). There were 9 pts positive for ER, PR, or Her2 and refractory to targeted agents, and 7 pts with conversion to triple-negative disease from pathology previously positive for ER, PR or Her2. Pts were heavily pre-treated, having received a median of 5 prior lines of systemic therapy. All but 3 patients had received previous systemic treatment with a taxane. Napabucasin + PTX was well tolerated. Grade 3 AE occurring in ≥ 5% patients was diarrhea (n = 4), and 1 pt had grade 4 diarrhea. The objective response rate (ORR), disease control rate (DCR), median progression free survival (mPFS), and median overall survival (mOS) for all pts and for each sub-group are summarized in the table. Conclusions: Napabucasin (BBI-608) plus weekly paclitaxel has demonstrated safety, tolerability, and encouraging signs of anti-cancer activity in pts with pretreated metastatic breast cancer. Further clinical evaluation of this combination regimen in controlled trials is warranted. Clinical trial information: NCT01325441. [Table: see text]
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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 | 0.004 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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".