Abstract P3-17-02: Influence of non-measurable disease on progression-free survival in patients with metastatic breast cancer
Bibliographic record
Abstract
Abstract Background: Progression free-survival (PFS) is the dominant endpoint in phase 3 randomized controlled trials (RCTs) in women with metastatic breast cancer (MBC), and requires the ability to measure target lesions. It is unknown whether treatment effect on PFS is consistent among patients with measurable and non-measurable disease. Methods: We searched MEDLINE, EMBASE and COCHRANE for phase 3 RCTs in MBC that reported outcomes in subgroups with non-measurable (or bone only disease, if not reported explicitly) and measurable disease. Data were extracted and a single hazard ratio (HR) and 95% confidence intervals (CI) were computed to compare the individual trial treatment effect in non-measurable versus measurable disease. Data were then pooled in a meta-analysis. We repeated the analysis comparing bone only to non-bone only disease and performed subgroup analyses based on drug mechanism of action. Results: Of 82 RCTs that enrolled patients with non-measurable disease, 16 trials comprising 8516 patients were eligible for analysis. All included RCTs used PFS or time to progression as primary endpoints. There was no difference in pooled treatment effect between patients with non-measurable and measurable disease (HR 1.01, 95% CI 0.89-1.15, p=0.82). However, compared to non-bone only disease, a significantly greater effect on PFS was seen in those with bone only disease (HR 0.82, 95% CI 0.70-0.98, p=0.03). Subgroups analyses according to drug mechanism are shown in Table 1 Intra-study comparison, according to evaluated drug mechanismCohort/ Investigational drugNo. studies includedMeasurable HR (95% CI)Non measurable HR (95% CI)Intra- study comparison HR (95% CI)P – for intra-study comparisonAll160.69 (0.65-0.73)0.72 (0.64-0.80)1.01 (0.89-1.15)0.82Chemotherapy30.99 (0.87-1.13)0.67 (0.44-1.02)0.73 (0.44-1.21)0.22Endocrine treatment40.86 (0.77-0.96)0.94 (0.80-1.10)1.13 (0.92-1.40)0.23Signal transduction inhibitors40.52 (0.48-0.57)0.41 (0.33-0.50)0.74 (0.59-0.94)0.01Anti-angiogenetic agents50.66 (0.59-0.73)0.84 (0.67-1.04)1.34 (1.05-1.71)0.02CI- confidence interval, HR- hazard ratio . Compared to patients with measurable disease, there was a greater effect on PFS in those with non-measurable disease in RCTs of signal transduction inhibitors and endocrine therapy (HR 0.74, 95% CI 0.59-0.94, p=0.01). There was a lesser effect on PFS in patients with non-measurable disease in RCTs of antiangiogenic drugs (HR 1.34, 95% CI 1.05-1.71, p=0.02). Comparable effect on PFS was shown in RCTs evaluating endocrine therapy and chemotherapy. Conclusions: There is variability in treatment effect on PFS in patients with measurable and non-measurable disease. There is greater effect on PFS in RCTs of endocrine therapy and signal transduction inhibitors and in patients with bone only disease. Standardization of PFS determination in patients with non-measurable and bone only disease is warranted. Citation Format: Goldvaser H, Ribnikar D, Fazelzad R, Seruga B, Templeton AJ, Ocana A, Amir E. Influence of non-measurable disease on progression-free survival in patients with metastatic breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-17-02.
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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 | 0.013 | 0.034 |
| Meta-epidemiology (narrow) | 0.002 | 0.000 |
| Meta-epidemiology (broad) | 0.008 | 0.020 |
| Bibliometrics | 0.002 | 0.003 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.003 | 0.002 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.003 | 0.003 |
| Insufficient payload (model declined to judge) | 0.008 | 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".