Metformin, placebo, and endocrine therapy discontinuation among participants in a randomized double-blind trial of metformin versus placebo in hormone receptor–positive early-stage breast cancer (CCTG MA32).
Bibliographic record
Abstract
526 Background: The MA32 study (NCT01101438) investigated whether 5-years of metformin improves invasive disease-free survival in early-stage breast cancer (BC). Non-adherence to endocrine therapy (ET) and medications for chronic conditions is common, and increases with drug toxicity and polypharmacy. This secondary analysis evaluates rates and predictors of early discontinuation of metformin, placebo, and ET among participants with HR positive BC. Methods: Patients with high-risk non-metastatic BC were randomized to 60 months of metformin (850 mg BID) or placebo. Patients were administered bottles of metformin/placebo every 180 days. Metformin/placebo compliance was defined as a bottle dispensed at month 48 or later (i.e., medication supplied for 54 months). The ET compliance analysis included patients with HR positive BC who received adjuvant ET with start and stop date reported and was defined as > 48 months of use. Associations of baseline covariates with drug compliance and with ET adherence were examined using multivariable models. Results: Among the 2,521 HR-positive BC patients, 32.9% were non-compliant to study drug. Non-compliance was higher among patients on metformin vs. placebo (37.1% vs. 28.7%, p<0.001). Reassuringly, compliance to ET was similar between treatment arms (28.4% vs 28.0%, p=0.86). Patients who were non-compliant to endocrine therapy, were more likely to be non-compliant to study therapy (38.8% vs. 30.1%, p<0.0001). In a multivariable analysis, study drug non-compliance was increased with metformin vs. placebo (OR=1.43, 95% CI, 1.21-1.70; p<0.0001); grade 1 or greater GI toxicity during the first year (70.9% vs. 53.2%; OR=1.20, 95% CI, 1.01-1.44; p=0.044); lower age (age < 50 OR = 1.44, 95% CI, 1.21 – 1.71; p<0.01) and higher body mass index (BMI > 30, OR=1.49, 95% CI, 1.25 - 1.77; p<0.0001). Study drug non-compliance was decreased with prior receipt of chemotherapy (OR = 0.68, 95% CI, 0.50–0.84; p<0.001). Non-compliance with endocrine therapy was associated with increased non-compliance to study drug (OR: 1.47, 95% CI, 1.20, 1.70, p < 0.0001). Study drug (metformin vs placebo) non-compliance was not associated with endocrine therapy non-compliance (OR=0.97, 95% CI, 0.80-1.17; p=0.74). Conclusions: While non-compliance was higher among patients on metformin, it was still considerable among patients on placebo. Among other factors, development of GI toxicity and non-adherence to ET were associated with non-adherence to study drug. Many BC patients on ET are prescribed metformin and other oral medications for the treatment of chronic conditions. Reassuringly, non-adherence to study drug did not impact endocrine therapy adherence. Attention to global medication adherence is needed to improve BC and cardiovascular outcomes in cancer survivors. Clinical trial information: NCT0110143.
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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 | 0.009 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.003 | 0.000 |
| 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".