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 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 | 0.003 | 0.001 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.002 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.002 | 0.002 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.004 |
| Insufficient payload (model declined to judge) | 0.008 | 0.002 |
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".