Abstract P6-18-15: Ribociclib + endocrine therapy in hormone receptor-positive, HER2-negative advanced breast cancer: A pooled safety analysis
Bibliographic record
Abstract
Abstract Background: In Phase III trials, ribociclib (RIB; cyclin-dependent kinase 4/6 inhibitor) + various endocrine therapy (ET) partners has demonstrated significantly prolonged progression-free survival vs placebo (PBO) + ET in patients (pts) with hormone receptor-positive (HR+), HER2-negative (HER2–) advanced breast cancer (ABC). Here we further evaluate the safety of RIB-based regimens of interest for the proposed indication (i.e. with a non-steroidal aromatase inhibitor [NSAI] or fulvestrant [FUL]) using pooled data from three Phase III trials (MONALEESA [ML]-2 [NCT01958021], -3 [NCT02422615], and -7 [NCT02278120]). Methods: Postmenopausal pts with HR+, HER2– ABC received RIB (600 mg/day; 3-weeks-on/1-week-off) or PBO + letrozole (LET; 2.5 mg/day; ML-2 [no prior ET for ABC]) or FUL (500 mg, Days 1 and 15 of Cycle 1, then Day 1 of every cycle thereafter; ML-3; no or ≤1 prior line of ET for ABC]). Premenopausal pts (ML-7; no prior ET and ≤1 chemotherapy for ABC]) received RIB or PBO + anastrozole (1 mg/day)/LET (2.5 mg/day) + goserelin (3.6 mg every 28 days). Adverse events (AEs) were characterized per Common Terminology Criteria for Adverse Events v4.03; safety analyses included time to first event, duration of event, and rate of associated RIB/PBO discontinuations. Results: Data for 1883 pts were pooled; 1065 pts received RIB + ET and 818 pts received PBO + ET (median exposure to study treatment: 17 and 13 months, respectively). Exposure-adjusted incidence rates for AEs of special interest were 561 and 131 per 100 pt-years in the RIB and PBO arms, respectively. The most common all-causality Grade 3/4 AEs (≥10% in any arm; RIB vs PBO) were neutropenia (59% vs 2%), leukopenia (18% vs 1%), and hypertension (13% vs 13%). A new Fridericia's corrected QT interval (QTcF) >480 ms occurred in (n/N) 52/1054 (5%) vs 11/814 (1%) pts in the RIB vs PBO arms; a new QTcF >500 ms occurred in 14/1054 (1%) vs 1/814 (<1%) pts. Median time to first event for Grade ≥2 neutropenia, elevated alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST), and QTc prolongation in the RIB arm was 2, 12, and 2 weeks, respectively; median duration of first Grade ≥2 event was 4, 4, and 2 weeks. In the RIB arm vs PBO arms, 7% vs 3% of pts discontinued study treatment due to AEs; common all-grade AEs leading to RIB/PBO discontinuation (≥2% in any arm) were elevated ALT (4% vs <1%) and elevated AST (2% vs 1%). Discontinuation due to QT prolongation occurred in 4 pts in the RIB arm and 2 in the PBO arm (both <1%). All-grade serious AEs occurred in 25% of pts in the RIB arm vs 15% of pts in the PBO arm. Conclusions: RIB in combination with various ET partners continues to demonstrate a predictable and manageable tolerability profile across a broad population of pts with HR+, HER2– ABC. Citation Format: Burris HA, Chan A, Im S-A, Chia S, Tripathy D, Esteva FJ, Campone M, Bardia A, Kong O, Bao W, Diaz-Padilla I, Rodriguez Lorenc K, Yardley DA. Ribociclib + endocrine therapy in hormone receptor-positive, HER2-negative advanced breast cancer: A pooled safety analysis [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-18-15.
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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 | 0.014 | 0.012 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.004 | 0.012 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.005 | 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".