Abstract P6-18-05: First-line ribociclib + endocrine therapy in hormone receptor-positive, HER2-negative advanced breast cancer: A pooled efficacy analysis
Bibliographic record
Abstract
Abstract Background: In three separate Phase III randomized, placebo-controlled trials, ribociclib (RIB; cyclin-dependent kinase 4/6 inhibitor) + various endocrine therapy (ET) partners prolonged progression-free survival (PFS) vs placebo (PBO) + ET in patients (pts) with hormone receptor-positive (HR+), HER2-negative (HER2–) advanced breast cancer (ABC). Here we further evaluate the efficacy of RIB-based regimens of interest (i.e. with a non-steroidal aromatase inhibitor [NSAI] or fulvestrant [FUL]) in pts who were ET-naïve in the ABC setting, using pooled data from three Phase III trials: MONALEESA (ML)-2 (NCT01958021; all pts), ML-3 (NCT02422615; no prior ET for ABC subgroup only), and ML-7 (NCT02278120; RIB + NSAI subgroup only). Methods: Postmenopausal pts with no prior ET for ABC received RIB (600 mg/day; 3-weeks-on/1-week-off) or PBO + either letrozole (2.5 mg/day) in ML-2 or FUL (500 mg every 28 days, with an additional dose on Day 15 of Cycle 1) in ML-3. In ML-7, premenopausal pts with no prior ET and ≤1 line of chemotherapy for ABC received RIB or PBO + goserelin (3.6 mg every 28 days) + NSAI (anastrozole [1 mg/day]/letrozole [2.5 mg/day]). The primary endpoint of all three trials was locally assessed PFS. Secondary endpoints included overall response rate (ORR), clinical benefit rate (CBR), and duration of response (DoR; ML-3 and -7). DoR was an exploratory endpoint in ML-2. Results: Data were pooled for 820 pts treated with RIB + ET (ML-2: n=334; ML-3: n=238; ML-7: n=248) and 710 pts treated with PBO + ET (ML-2: n=334; ML-3: n=129; ML-7: n=247). As of the data cutoffs (ML-2: January 2, 2017; ML-3: November 3, 2017; ML-7: August 20, 2017), in the RIB + ET vs PBO + ET arms, 385 (47%) vs 234 (33%) pts remained on-treatment; the most common reason for discontinuation was disease progression (n=292 [36%] vs n=391 [55%]). In this pooled analysis, median PFS was prolonged for RIB + ET vs PBO + ET, with a hazard ratio of 0.570 (95% confidence interval [CI] 0.491–0.662); median PFS was 25.3 months (95% CI 23.9–29.6) vs 15.6 months (95% CI 14.4–16.9), respectively. Consistent PFS benefit for RIB + ET vs PBO + ET was observed across pt subgroups, including ECOG performance status, age, race, or presence/absence of liver and/or lung metastases or bone-only disease. Among all pts in the pooled analysis, the ORR was 41% for RIB + ET vs 28% for PBO + ET and the CBR was 79% vs 70%, respectively. In pts with measurable disease at baseline (RIB + ET: n=639; PBO + ET: n=542), the ORR was 51% for RIB + ET vs 37% for PBO + ET and the CBR was 79% vs 68%, respectively. In the RIB + ET vs PBO + ET arms, the median DoR was 26.7 months vs 20.0 months. A decrease in best percentage change from baseline in the sum of longest diameters per RECIST was observed in 86% of pts receiving RIB + ET vs 73% of pts receiving PBO + ET. Conclusions: RIB in combination with various ET partners demonstrates improved clinical outcomes vs PBO + ET across a broad population of pts with HR+, HER2– ABC. These data provide further support for the use of RIB-based combinations in pre- and postmenopausal pts with HR+, HER2– ABC who have received no prior ET for advanced disease. Citation Format: Tripathy D, Hortobagyi G, Chan A, Im S-A, Chia S, Yardley D, Esteva FJ, Hurvitz S, Kong O, Bao W, Rodriguez Lorenc K, Diaz-Padilla I, Slamon DJ. First-line ribociclib + endocrine therapy in hormone receptor-positive, HER2-negative advanced breast cancer: A pooled efficacy 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 P6-18-05.
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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 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.005 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.002 |
| Insufficient payload (model declined to judge) | 0.009 | 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".