Results of a phase II trial of trastuzumab (H) and pertuzumab (P) in patients (pts) with HER2-positive metastatic breast cancer (MBC) who had progressed during trastuzumab therapy
Bibliographic record
Abstract
1026 Background: P is a humanized monoclonal antibody that binds to the specific dimerization epitope of HER2, blocking HER2 homo- and heterodimerization, thus preventing signal transduction. Xenograft studies indicate that the complementary mechanisms of action of P and H have a synergistic effect. Methods: This single-arm, Simon-type, two-stage phase II trial included pts with measurable, centrally tested HER2-positive MBC, ≥3 lines of prior therapy (including adjuvant therapy), disease progression during prior H therapy, and a baseline LVEF ≥55% that had not declined to <50% with H therapy. Consenting pts received H at 2 mg/kg qw (4 mg/kg loading dose [LD]) or 6 mg/kg q3w (8 mg/kg LD) plus P at 420 mg q3w (840 mg LD) starting within 9 weeks of the last dose of H. LVEF was assessed regularly in all pts. The primary endpoint was objective response and clinical benefit response rate (OR and SD ≥6 mths). Results: 66 pts have been enrolled and all have received ≥2 doses of study medication (41 are still on treatment). 63 pts have experienced ≥1 AE. Frequent AEs of all causes included diarrhea (63%), pain (35%), nausea/vomiting (30%), mucositis (32%), skin (27%), and rash (26%). Only 3 treatment-related AEs of severity G3, and none of G4, have been observed (diarrhea, pruritic rash due to contrast dye allergic reaction and a central line infection), all of which resolved and treatment continued. In addition 1 pt had a protocol-defined AE of special significance; an asymptomatic fall in LVEF of ≥10%-<50% based on a local reading which was not centrally confirmed. This pt was withdrawn due to progressive disease. No pts withdrew due to treatment-related or cardiac AEs. Preliminary RECIST response data (Baselga, ASCO 2007) are as follows: objective responses were seen in 6 of the 33 evaluable pts (1 CR, 5 PRs). Additionally, 7 pts achieved SD ≥6 mths and 10 pts SD <6 mths. Conclusions: The combination of H and P was well tolerated and active in pts with MBC whose disease had progressed during therapy with H. Biomarker data from this study are being analyzed. Further studies in pts with MBC and early breast cancer are ongoing. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Roche Roche, sanofi-aventis Roche F. Hoffmann-La Roche, Roche, sanofi-aventis F. Hoffmann-La Roche, Roche, Roche Canada Roche
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How this classification was reachedexpand
Direct model labels (unvalidated)
Per-model category and study-design labels from the labeling rounds. They are machine output, unvalidated, and the disagreement between models ships as data. No study design here is MEDLINE-validated yet.
| Model arm | Categories | Study design | Confidence |
|---|---|---|---|
| gemma | no category Domain: not available · Genre: Empirical About the Canadian research system: no · About a Canadian topic: no | Non-randomized trial | low |
| gpt | no category Domain: not available · Genre: Empirical About the Canadian research system: no · About a Canadian topic: no | Non-randomized trial | medium |
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 | 0.003 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.003 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| 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) | 0.000 | 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, unvalidatedLabeled directly by 2 models reading the full record.
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".