In-depth gene expression analysis of premenopausal patients with HR+/HER2− advanced breast cancer (ABC) treated with ribociclib-containing therapy in the Phase III MONALEESA-7 trial.
Bibliographic record
Abstract
1018 Background: The Phase III MONALEESA-7 study (NCT02278120) is the first dedicated trial of endocrine therapy (ET) ± a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor in premenopausal patients (pts) with hormone receptor–positive (HR+)/human epidermal growth factor receptor 2–negative (HER2−) ABC. The study demonstrated that the addition of ribociclib (RIB) to a nonsteroidal aromatase inhibitor (NSAI) or tamoxifen (TAM) + goserelin (GOS) significantly extended progression-free survival (PFS; hazard ratio [HR] 0.55; Tripathy D, et al. Lancet Oncol. 2018). Here we present a gene expression analysis of baseline tumor mRNA from MONALEESA-7. Methods: Premenopausal pts with HR+/HER2− ABC were treated with RIB or placebo (PBO) + GOS with either an NSAI (letrozole or anastrozole) or TAM. Baseline archival tumor samples from 360 of 672 intent-to-treat (ITT) pts were evaluated for gene expression (RIB n = 185; PBO n = 175) using a customized NanoString nCounter® GX 800-gene panel containing relevant breast cancer, CDK, and proliferation pathway–related genes. Pt subgroups were classified as having low or high mRNA expression using median expression as the cutoff. Results: PFS benefit in the biomarker-assessed group was similar to that in the ITT population. A trend toward a more pronounced PFS benefit with RIB was observed in pts with high vs low expression of CCND1 (HR 0.38 vs 0.67, respectively), IGF1R (HR 0.33 vs 0.77), and ERBB3 (HR 0.33 vs 0.76). The PFS benefit seen with RIB also trended to be greater in pts with low vs high expression of CCNE1 (HR 0.38 vs 0.65, respectively) and MYC (HR 0.37 vs 0.69). The PFS benefit with RIB was similar in pts with high vs low expression of FGFR1 (HR 0.45 vs 0.61, respectively), ESR1 (HR 0.57 vs 0.57), and tumor proliferation genes, such as MKI67 (HR 0.50 vs 0.51). Conclusions: This is the first gene expression analysis of a large set of premenopausal pts with ABC. The benefit with RIB was generally consistent across gene expression subgroups, although the magnitude varied in certain subsets. This analysis suggests that there may be unique resistance mechanisms to ET ± CDK4/6 inhibitors in premenopausal pts with ABC. Clinical trial information: NCT02278120.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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 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".