A randomized phase II study (VEG108838) of lapatanib plus pazopanib (L+P) versus lapatanib (L) in patients with ErbB2+ inflammatory breast cancer (IBC).
Bibliographic record
Abstract
531 Background: ErbB2 amplification is frequently reported in IBC and there is evidence of positive association between ErbB2 and VEGF expression. We evaluated the combination of anti ErbB2 and VEGF therapy in ErbB2+ IBC. Methods: We conducted a multicenter, randomized clinical trial for patients (pts) with relapsed ErbB2+ IBC. Cohort 1: Pts stratified (prior trastuzumab; cutaneous disease only vs systemic) and randomized 1:1 to receive L 1500 mg + placebo or L 1500 mg + P 800 mg, QD. Due to high incidence of Grade 3/4 diarrhea in pts treated with L 1500 mg+ P 800 mg in another study, Cohort 1 was closed after 76 pts randomized. Cohort 2 (87 pts ): Pts were stratified (prior trastuzumab) and randomized 5:5:2 to receive L 1500 mg + placebo or L 1000 mg + P 400 mg (double-blind) or P 800 mg (open-label), respectively, QD. Treatment continued until PD, unacceptable toxicity or death. Primary endpoint was ORR. Secondary endpoints included PFS, OS, and safety. Results: Cohort 1: 76 pts were randomized and treated: L, n=38; L+P, n=38. ORR was 29% for the L arm, and 45% for the L+P arm. Median PFS was 16.1 and 14.3 wks, respectively, for the L and L+P arms. The most frequent Grade ≥3 AEs were diarrhea (0% vs 18%) vomiting (0% vs 8%), ALT increased (0% vs 8%), neutropenia (3% vs 13%), and bilirubin increased (0% vs 5%). Dose reductions due to AE were 3% and 21% and dose interruptions due to AE were 11% and 55% in the L and L+P arms, respectively. Cohort 2: 88 pts were randomized (87 treated): L, n=36; P, n=14; L+P, n=38. The ORR was 47%, 31%, and 58% for the L, P, and L+P arms, respectively. Median PFS was 16.0, 11.4, and 16.0 wks for the L, P, and L+P arms, respectively. The most frequent Grade ≥3 AEs were ALT increased (0%, 0%, 21%), AST increased (0%, 0%, 18%), diarrhea (3%, 8%, 8%), and fatigue (3%, 8%, 8%). Dose reductions due to AE occurred in 0%, 0%, and 13% of pts and dose interruptions due to AE occurred in 22%, 23%, and 39% of pts in the L, P, and L+P arms, respectively. Conclusions: This prospective, randomized study confirmed the clinical activity of lapatinib single agent in metastatic ErbB2+ IBC. Furthermore, we demonstrated increased toxicity associated with the combination without a clinically meaningful improvement in efficacy.
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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 | 0.002 | 0.002 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.007 | 0.001 |
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".