A double-blind placebo controlled randomized phase III trial of fulvestrant and ipatasertib as treatment for advanced HER2-negative and estrogen receptor positive (ER+) breast cancer following progression on first line CDK 4/6 inhibitor and aromatase inhibitor: The CCTG/BCT MA.40/FINER study (NCT04650581).
Bibliographic record
Abstract
LBA1005 Background: Standard first line therapy in ER+/ HER2 negative endocrine sensitive metastatic breast cancer (MBC) is a CDK4/6 inhibitor plus AI. Upon progression the majority of patients will receive further endocrine based therapy. Alterations in PI3K/AKT pathway genes are a known mechanism of endocrine resistance – either de novo or acquired. The MA.40 trial evaluated the efficacy and safety of the AKT inhibitor ipatasertib versus placebo plus fulvestrant in the metastatic breast cancer (MBC) setting immediately post progression on 1 st line CDK4/6 inhibitor and AI. Methods: This phase III, randomized, double-blind trial enrolled pre/peri/postmenopausal women and men with ER+/HER-2 negative MBC. Patients were randomly assigned 1:1 to receive ipatasertib plus fulvestrant versus (vs) placebo plus fulvestrant. Stratification factors included: AKT pathway altered ( PIK3CA , AKT1 , and/or PTEN genomic alteration(s)) vs wild-type/unknown and endocrine resistance (primary vs secondary). Primary objective: To compare investigator assessed PFS (RECIST 1.1) between treatment arms in the ITT population. Pre-specified secondary analysis: PFS in the AKT pathway altered cohort using a hierarchical procedure. The FoundationOne Liquid cfDNA NGS assay was utilized to assess genomic alterations in the AKT pathway for stratification. Results: 250 participants (females 247/males 3) were enrolled from Canada, Australia and New Zealand between January 2021 and May 2024. Baseline characteristics between arms were balanced. 44.4% of the study population had AKT pathway alteration(s) per cfDNA assay. Median follow-up 15.2 months(mo); proportion remaining on protocol treatment at time of analysis 21.0% ipatasertib vs 11.3% placebo arm. Median PFS ITT ipatasertib vs placebo arms were: 5.32 mo (95% CI: 3.58 to 5.62 mo) vs 1.94 mo (95% CI: 1.84 to 3.22 ) [HR 0.61, 95% CI: 0.46 to 0.81; p= 0.0007] and in the AKT pathway altered cohort: 5.45 mo (95% CI: 3.55 to 11.01 ) vs 1.91 mo (95% CI: 1.77 to 3.48) [HR = 0.47, 95% CI: 0.31 to 0.72; p= 0.0005]. Grade 3 or higher adverse events (AE) ipatasertib vs placebo arms (%):37.1 vs 27.4. Grade 3 or higher non haematological treatment related AE > 1% ipatasertib vs placebo arms: diarrhea (16% vs 0%); fatigue (3% vs 0%); vomiting (2% vs 0), rash (2% vs 0%). Treatment discontinuation due to AEs ipatasertib vs placebo arms: 6.5% vs 0.8%. Conclusions: Ipatasertib plus fulvestrant significantly prolongs PFS compared to placebo/fulvestrant in patients with hormone receptor–positive MBC post progression on 1 st line CDK 4/6 inhibitor and AI. Follow-up and additional analyses continue. Supported by Hoffmann-La Roche Ltd, CCS grant #707213. Clinical trial information: NCT04650581 .
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.003 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.004 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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".