Associations with response to poly (ADP-ribose) polymerase (PARP) inhibitors in metastatic breast cancer: Results of a meta-regression analysis.
Bibliographic record
Abstract
e12567 Background: PARP inhibitors (PARPi), when given as single agents, have modest antitumor activity in patients with advanced breast cancer and germline mutation in BRCA1 or BRCA2. It is unclear whether some subgroups derive greater benefit from treatment. Methods: Two electronic databases (MEDLINE, CENTRAL) and one registry (Clinicaltrials.gov) were searched from inception to November 2018 to identify trials of PARPi in patients with metastatic breast cancer. The response rates to PARPi were extracted and pooled. Analyses were performed for patients with a germline BRCA mutation. Meta-regression explored the influence of patient and tumor characteristics and previous chemotherapy on the objective response rate (ORR) as reported in individual studies. Analysis comprised of a linear regression weighted by individual study sample size using the weighted least squares (mixed effect) method. Quantitative significance was defined using methods described by Burnand et al. Results: Of 1855 citations, 11 studies comprising 813 patients were included in the analysis. 765 (94%) patients had a germline BRCA mutations; 48% of breast cancers were triple-negative. 76% of patients had received at least 1 previous line of chemotherapy in the metastatic setting and 30% were exposed to platinum-based chemotherapy. Pooled ORR was 47% in patients with a germline BRCA mutation. Meta-regression showed that previous chemotherapy in the metastatic setting ( = -0.94, p = 0.006), especially platinum-based chemotherapy ( = -0.89, p = 0.02) were associated with highly significant negative association with ORR. A highly quantitatively significant negative association was observed for age ( = -0.80, p = 0.10), but this did not meet statistical significance. Performance status ( = 0.44, p = 0.38) and hormone receptor status (hormone receptors positive: = 0.46, p = 0.30) were not associated with response. Conclusions: PARPi therapy is associated with lesser response in patient with prior chemotherapy exposure, especially platinum-based treatment. Younger patients may benefit more from PARPi. There was no association between ORR and hormone receptor status.
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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 | 0.026 | 0.035 |
| Meta-epidemiology (narrow) | 0.004 | 0.002 |
| Meta-epidemiology (broad) | 0.015 | 0.080 |
| Bibliometrics | 0.006 | 0.008 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.003 | 0.002 |
| Open science | 0.003 | 0.002 |
| Research integrity | 0.003 | 0.003 |
| Insufficient payload (model declined to judge) | 0.004 | 0.001 |
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".