Results of an interim analysis of a multinational randomized, double-blind, phase III study in patients (pts) with previously treated metastatic colorectal cancer (mCRC) receiving FOLFOX4 and PTK787/ZK 222584 (PTK/ZK) or placebo (CONFIRM 2)
Bibliographic record
Abstract
3508 Background: PTK/ZK is a novel, oral, small molecule, antiangiogenic compound that inhibits tyrosine kinase signaling of all known vascular endothelial growth factor (VEGF) receptors. Methods: 855 pts were randomized to FOLFOX4 plus PTK/ZK (1250 mg, qd), or placebo. Eligibility included histologically or cytologically documented mCRC, pretreatment for metastatic disease with irinotecan/fluoropyrimidine-based chemotherapy, measurable disease by RECIST, PS of 0–2 and adequate organ and bone marrow function. The primary endpoint is overall survival (OS). Secondary endpoints included OS and PFS in high LDH pts (stratifiedbybaseline serum LDH levels > 1.5 × ULN). Results: OS was 12.1 mo in the PTK/ZK arm and 11.8 mo in the placebo arm (HR: 0.94; p=0.511). A pre-planned triangular test suggested a low probability of demonstrating an improvement in OS at the final analysis (4Q 2006). The response rates (CR+PR) were 18.5% in the PTK/ZK arm, 17.5% in the placebo arm. PFS was significantly longer in the PTK/ZK arm (5.5 mo vs. 4.1 mo; HR: 0.83; p=0.026). LDH, usually a poor prognostic factor in mCRC, is predictive of the outcome in the PTK/ZK arm. Pts with high LDH showed a strong improvement in PFS when treated with PTK/ZK (5.6 mo vs. 3.8 mo; HR: 0.63; p<0.001) and an improved OS (9.6 mo vs. 7.5 mo; HR: 0.78; p=0.10). Adverse events (AE) were similar to that of the CONFIRM 1 trial (ASCO 2005). Most frequent grade 3/4 AE associated with PTK/ZK were hypertension (PTK/ZK: 21%; placebo: 5%), diarrhea (16%; 8%), fatigue (14.5%; 6.9%), nausea (11%; 5%), vomiting (9%; 5%), dizziness (9%; 1%). AEs were generally reversible. Thrombotic and embolic events of all grades occurred in 6% (PTK/ZK) vs. 1% (placebo) and 4% vs. 1%, respectively. There was no increase in bowel perforations, hematological toxicities or peripheral neuropathy in the PTK/ZK arm. Conclusions: While the primary endpoint for OS was not met, PTK/ZK improves PFS significantly in the overall population, and shows strong activity in patients with high baseline serum LDH. [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 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.004 | 0.000 |
| 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 | 0.000 |
| 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".