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Abstract P2-08-02: Progression-free survival results in patient subgroups from a Phase 3 randomized trial of fulvestrant 500 mg vs anastrozole for hormone receptor-positive advanced breast cancer (FALCON)

2017· article· en· W2593142478 on OpenAlexaboutno aff
J.F.R. Robertson, S Noguchi, Zhimin Shao, LM Grinsted, M.A. Fazal, MJ Ellis

Bibliographic record

VenueCancer Research · 2017
Typearticle
Languageen
FieldMedicine
TopicAdvanced Breast Cancer Therapies
Canadian institutionsnot available
Fundersnot available
KeywordsAnastrozoleFulvestrantMedicineInternal medicineClinical endpointHazard ratioOncologyMetastatic breast cancerBreast cancerProgression-free survivalRandomized controlled trialCancerEstrogen receptorTamoxifenConfidence intervalChemotherapy

Abstract

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Abstract BACKGROUND Improved efficacy was suggested for fulvestrant 500 mg, a selective estrogen receptor degrader (SERD), vs anastrozole as first-line treatment for hormone receptor-positive locally advanced or metastatic breast cancer (LA/MBC) in the open-label Phase 2 FIRST trial. The Phase 3, randomized, double-blind, multicenter FALCON trial (NCT01602380) compared fulvestrant 500 mg with anastrozole 1 mg in patients with hormone receptor-positive LA/MBC who had not received prior hormonal therapy. The primary endpoint of the study was met, such that there was a statistically significant improvement in progression-free survival (PFS) for fulvestrant 500 mg vs anastrozole. We present an analysis of PFS for pre-specified patient subgroups in the FALCON trial. METHODS Eligible patients had ER and/or progesterone receptor (PgR)-positive breast cancer, WHO performance status 0–2 and ≥1 measurable/non-measurable lesion(s). Patients were randomized (1:1) to receive fulvestrant 500 mg (IM on Days 0, 14, 28, and each 28 days thereafter) or anastrozole 1 mg daily. The primary endpoint was PFS, assessed via RECIST 1.1, surgery/radiotherapy for disease worsening, or death (any cause). PFS was evaluated in patient subgroups defined by pre-specified baseline covariates. The consistency of effect across patient subgroups was assessed via hazard ratios and 95% confidence intervals using a log-rank test. RESULTS Overall, 462 patients were randomized to treatment: 230 received fulvestrant 500 mg and 232 received anastrozole. PFS outcomes in each patient subgroup are presented in the Table. CONCLUSIONS This analysis of patient subgroups from the FALCON trial suggests that treatment effects were largely consistent across the subgroups analyzed with some possible exceptions (e.g. patients with visceral vs non-visceral disease). Further work is ongoing to understand the possible treatment effect in these subgroups. PFS in pre-specified patient subgroupsSubgroup Number of patients (%) with event Hazard ratio (95% CI) Fulvestrant 500 mg n=230 Anastrozole n=232 Breast cancer type Locally advanced11/28 (39.3%)14/32 (43.8%)0.79 (0.36, 1.73)Metastatic132/202 (65.3%)152/200 (76.0%)0.78 (0.62, 0.99)Prior chemotherapy for LA/MBC Yes31/36 (86.1%)33/43 (76.7%)1.08 (0.66, 1.77)No112/194 (57.7%)133/189 (70.4%)0.75 (0.59, 0.97)Geographic regiona US/Canada16/25 (64.0%)19/24 (79.2%)0.66 (0.34, 1.30)Non-US/Canada127/205 (62.0%)147/208 (70.7%)0.81 (0.64, 1.03)Measurable disease Yes124/193 (64.2%)143/196 (73.0%)0.76 (0.60, 0.97)No19/37 (51.4%)23/36 (63.9%)0.99 (0.53, 1.82)ER-positive and PgR-positive Yes103/175 (58.9%)127/179 (70.9%)0.73 (0.56, 0.94)No40/55 (72.7%)39/53 (73.6%)1.04 (0.67, 1.62)Bisphosphonate use at baseline Yes44/61 (72.1%)53/62 (85.5%)0.69 (0.46, 1.03)No99/169 (58.6%)113/170 (66.5%)0.82 (0.63, 1.07)Visceral disease Yes92/135 (68.1%)87/119 (73.1%)0.99 (0.74, 1.33)No51/95 (53.7%)79/113 (69.9%)0.59 (0.42, 0.84)ªData for Asia/non-Asia subgroups are presented in a separate abstract Citation Format: Robertson JFR, Noguchi S, Shao Z, Grinsted LM, Fazal M, Ellis MJ. Progression-free survival results in patient subgroups from a Phase 3 randomized trial of fulvestrant 500 mg vs anastrozole for hormone receptor-positive advanced breast cancer (FALCON) [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-08-02.

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How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.003
metaresearch head score (Gemma)0.002
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Randomized trial · Consensus signal: Randomized trial
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.210
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0030.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0020.000
Bibliometrics0.0000.000
Science and technology studies0.0000.001
Scholarly communication0.0000.001
Open science0.0010.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0000.000

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.

Opus teacher head0.049
GPT teacher head0.424
Teacher spread0.375 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

Study designRandomized trial
Domainnot available
GenreEmpirical

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".

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Citations4
Published2017
Admission routes1
Has abstractyes

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