Abstract 4718: A randomized phase 2 study of the cyclin-dependent kinase (CDK) inhibitor dinaciclib (SCH 727965) in patients with advanced breast cancer
Bibliographic record
Abstract
Abstract Dinaciclib is a potent, selective inhibitor of CDKs 1, 2, 5, and 9 with preclinical activity in breast cancer cell lines and tumor xenografts. A randomized, multicenter, open-label phase 2 study was conducted to compare the efficacy of dinaciclib and capecitabine (1250 mg PO) in patients (pts) with advanced, previously treated breast cancer (BC). Dinaciclib 50 mg/m2 was administered by 2-hour i.v. infusion once every 21 days. Key inclusion criteria included ≤2 prior chemotherapy regimens, prior treatment with a taxane and anthracycline, and measurable disease. According to the original design, 20 pts were to be randomized 1:1 and thereafter pts were to be randomized using an adaptive Bayesian algorithm that adjusts the randomization ratio in favor of the more active arm. The protocol was amended to continue 1:1 randomization in lieu of the adaptive approach to obtain more experience with upfront dinaciclib. Patients were allowed to cross-over to dinaciclib after progressing on capecitabine. This design provides a comparison of dinaciclib versus capecitabine and an assessment of dinaciclib activity in patients who progressed on capecitabine. Time-to-progression (TTP) was the primary endpoint for pts receiving upfront treatment, and response rate (RR) was the primary endpoint for pts who crossed over to dinaciclib. Twenty-eight pts were treated (13 dinaciclib, 15 capecitabine). Data on 19 dinaciclib treated pts, including 6 that crossed over, are presented. Their median age was 53 (34-80) with a median of 2 (1-2) prior chemotherapy regimens and median ECOG performance status of 1(0-1). ER+/PR+/Her2 receptor status is available for 10/13 pts treated with dinaciclib, including five with ER+/PR+/Her2-, one with ER-/PR-/Her2-, two with ER-/PR-/Her2+ and two with ER+/PR-/Her2-. The median number of treatment cycles was 3 (1-11). 17 pts received more than one cycle of dinaciclib treatement. Investigators reported partial responses (PR) in 2/12 (17%) evaluable subjects receiving upfront dinaciclib; both with ER+/HER2- tumors. One confirmed PR had a complete resolution of a 4 cm chest wall mass. No responses were reported on the cross over arm. Four of fifteen (27%) evaluable subjects receiving capecitabine were reported to have PR. Analysis of TTP will be presented at the meeting. Treatment-related grade 1 and 2 toxicities, occurring in >30% of pts, included diarrhea (67%), nausea (67%), vomiting (61%), neutropenia (50%) and decreased appetite (44%). The most common treatment-related grade 3 and 4 toxicities, occurring in 2 or more pts, were neutropenia (64%), leukopenia (29%), AST increased (14%) and febrile neutropenia (14%). PK results will be included in the final abstract. Dinaciclib monotherapy showed some anti-tumor activity, with acceptable safety and tolerability, in patients with ER+/Her2- BC, warranting further exploration in the combination setting. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4718. doi:10.1158/1538-7445.AM2011-4718
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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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".