Alpelisib (ALP) + fulvestrant (FUL) in patients (pts) with <i>PIK3CA-</i>mutated (mut) hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2–) advanced breast cancer (ABC) previously treated with cyclin-dependent kinase 4/6 inhibitor (CDKi) + aromatase inhibitor (AI): BYLieve study results.
Bibliographic record
Abstract
1006 Background: PIK3CA mutations (mut) occur in ~40% of pts with HR+, HER2– ABC and are associated with poor prognosis and resistance to treatment (tx). ALP, a PI3Kα inhibitor, plus FUL demonstrated efficacy in the phase 3 SOLAR-1 trial of HR+, HER2– PIK3CA-mut ABC. Little clinical data and few prospective studies are available to inform tx decisions for pts with HR+, HER2– PIK3CA-mut ABC in the post-CDKi setting. BYLieve is the first trial evaluating ALP + endocrine therapy (ET; FUL or letrozole) in pts with HR+, HER2– PIK3CA-mut ABC who progressed on/after prior therapy, including CDKi. In this ongoing phase 2, open-label, noncomparative study, 112 pts with centrally confirmed PIK3CA mut in tumor tissue are enrolled in each cohort per immediate prior tx of CDKi + AI, CDKi + FUL, or systemic chemo or ET. Enrollment is complete in prior CDKi + AI and CDKi + FUL cohorts and ongoing in prior systemic chemo or ET cohort. We report on the cohort of pts with CDKi + AI as immediate prior tx. Methods: Pts received ALP 300 mg/day + FUL 500 mg Q28D + C1D15. Primary endpoint was proportion of pts alive without disease progression at 6 mo per local assessment; 2-sided 95% confidence intervals (CI) were calculated using Clopper and Pearson (1934) exact method. Evidence of clinically meaningful tx effect was defined as the lower bound of the 95% CI > 30%. Safety was assessed in all patients; AEs presented by preferred term. Results: 127 pts whose immediate prior tx was CDKi + AI were enrolled, of whom 121 had centrally confirmed PIK3CA mut; median follow-up was 11.7 mo. Primary endpoint was met: proportion of pts without disease progression at 6 mo was 50.4% (95% CI, 41.2-59.6). Most frequent all-grade AEs were diarrhea (60%), hyperglycemia (58%), nausea (46%), fatigue (29%), decreased appetite (28%), and rash (28%). Most frequent grade ≥3 AEs included hyperglycemia (28%), rash (9%), and rash maculopapular (9%). Incidence of AEs leading to discontinuation was low; most frequent AEs leading to discontinuation were rash (5 pts, 3.9%), colitis, hyperglycemia, urticaria, and vomiting (2 pts, 1.6% each). Conclusions: With follow-up still ongoing, BYLieve shows in a large number of pts that ALP + FUL demonstrates clinically meaningful efficacy and manageable toxicity post CDKi tx. Building on findings from SOLAR-1, BYLieve further supports use of ALP + FUL for HR+, HER2– PIK3CA-mut ABC. 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 | 0.002 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.005 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.004 |
| 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".