Phase II randomized study of the EGFR, HER2, HER3 signaling inhibitor AZD8931 in combination with anastrozole (A) in women with endocrine therapy (ET) naive advanced breast cancer (MINT).
Bibliographic record
Abstract
531 Background: Preclinical data suggest a key role for EGFR inhibition in delaying acquired resistance to ET in ER+ breast cancer (BC). Retrospective analyses of 2 Phase II studies suggested adding gefitinib to ET delayed PFS in ET naive (ETN) BC. This randomized, double-blind, placebo-controlled multi-center study (NCT01151215) was conducted to prospectively test the hypothesis that adding AZD8931, an inhibitor of EGFR, HER2 and HER3 signaling, to A would be beneficial in delaying endocrine resistance in an advanced ETN BC population. Methods: Post-menopausal women with ER+ and/or PR+, ETN, HER2-negative, advanced BC were randomized (1:1:1) to receive A (1 mg od) plus AZD8931 20 or 40 mg bd or placebo (P). The primary endpoint was PFS (ITT population). Data presented are from an interim analysis (data cutoff 31 Aug 2012; 39% pts had a progression event). Results: Between Jun 2010 and Jun 2012, 359 pts (median age 61 years) were randomized to A combined with AZD8931 20 mg (n=118), 40 mg (n=120) or P (n=121). At the interim analysis, median PFS in the AZD8931 20 mg, 40 mg and P arms was 10.9, 13.8 and 14.0 months, respectively; PFS HR (95% CI) for AZD8931 20 mg:P was 1.37 (0.91–2.06, P=0.135) and for AZD8931 40 mg:P was 1.16 (0.77–1.75, P=0.485). Deaths were reported for 20 (17%), 16 (13%) and 12 pts (10%) in the AZD8931 20 mg, 40 mg and P arms, respectively. Grade ≥3 AEs were reported for 22 (19%), 44 (37%) and 18 (15%) pts in the AZD8931 20 mg, 40 mg, and P arms, respectively, the most frequent being rash (0% vs 8% vs 2%), acneiform dermatitis (0% vs 7% vs 0%) and hypertension (3% vs 3% vs 2%). Serious AEs were reported for 12%, 14% and 9% pts in the AZD8931 20 mg, 40 mg and P arms, respectively, and discontinuation (of AZD8931 or P) due to an AE in 5%, 8% and 2% pts, respectively. Conclusions: Co-blockade of EGFR, HER2, HER3 in combination with aromatase inhibition does not appear to delay endocrine resistance to ETN BC. Based on the low probability of demonstrating superior efficacy with addition of AZD8931 to A and the overall risk/benefit, the study was closed at the recommendation of the IDMC and pts discontinued AZD8931. Clinical trial information: NCT01151215.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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) | 0.003 | 0.001 |
| Bibliometrics | 0.001 | 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) | 0.006 | 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".