BYLieve: A phase II study of alpelisib (ALP) with fulvestrant (FUL) or letrozole (LET) for treatment of <i>PIK3CA</i> mutant, hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2<i>–</i>) advanced breast cancer (aBC) progressing on/after cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) therapy.
Bibliographic record
Abstract
TPS1107 Background: Endocrine therapy (ET) is the standard of care for treatment of HR+, HER2– aBC. However, ET resistance occurs frequently due to dysregulation of the PI3K/AKT/mTOR pathway, specifically mutations in PIK3CA, the gene encoding the p110alpha subunit of PI3K. In a phase 1 study, ALP, a PI3Kα-specific inhibitor, in combination with FUL has shown antitumor activity in patients (pts) with PIK3CA mutant, HR+, HER2– aBC. The ongoing phase 3 SOLAR-1 trial (NCT02437318) is evaluating ALP + FUL combination in HR+, HER2– aBC. The present BYLieve study aims to assess the efficacy and safety of ALP + FUL/LET in PIK3CA-mutant, HR+, HER2– aBC progressing on/after prior CDK4/6i combination therapy. Methods: BYLieve is a phase 2, multicenter, open-label, 2-cohort, non-comparative study. Men and women (pre-menopausal and post-menopausal; ≥18 years) with PIK3CA-mutant, HR+, HER2− locally advanced or metastatic breast cancer that has progressed on/after prior CDK4/6i combination therapy are eligible. Other eligibility criteria include ≥1 measurable lesion (RECIST v1.1) or predominantly lytic bone lesion; ECOG PS ≤2; ≤1 line of prior chemotherapy in the advanced setting; and no prior PI3K inhibitor therapy. Pts are allocated to 2 cohorts; cohort A (pts who had received CDK4/6i + aromatase inhibitor): oral ALP (300 mg QD) + intramuscular FUL (500 mg) and cohort B (pts who had received CDK4/6i + FUL): oral ALP (300 mg QD) + oral LET (2.5 mg QD). The primary end point is the proportion of pts who are alive without disease progression at 6 months (RECIST v1.1; local assessment), and will be evaluated separately in each cohort. Evidence of treatment effect will be demonstrated if the lower bound of the 90% CI is greater than 30% with a planned sample size of 80 pts in each cohort. Secondary end points include progression-free survival (PFS), PFS on next-line treatment (PFS2), overall response rate, clinical benefit rate, duration of response, safety, and tolerability. Recruitment of the planned 160 pts is currently ongoing. Clinical trial information: NCT03056755.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.004 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.001 |
| 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, 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".