Serum PD-L1 and outcomes in CCTG MA.31 phase 3 trial of anti-HER2 therapy in first-line HER2+ metastatic breast cancer patients (trastuzumab arm only).
Bibliographic record
Abstract
1031 Background: In MA.31 the lapatinib-taxane combination led to shorter PFS than trastuzumab-taxane in HER2+ metastatic breast cancer. We previously reported the positive prognostic utility of pretreatment serum PD-L1 in 63 trastuzumab-treated patients (ASCO 2017, #1024), and here we evaluated it in the trastuzumab arm of MA.31. Methods: MA.31 accrued 652 centrally and/or locally-identified HER2-positive patients; in the trastuzumab arm 186 patients had pretreatment serum available.TheELLA immunoassay platform (ProteinSimple, San Jose, CA) was used to quantitate serum PD-L1. Stratified step-wise forward Cox multivariate analysis was used for PFS and OS. Results: In univariate analysis for PFS, serum PD-L1 was not a significant biomarker for PFS. In univariate analysis for OS, higher serum PD-L1 was a significant biomarker for shorter OS (continuous PD-L1: HR 3.86, p = 0.044; quartiles of PD-L1: HR 1.55, p = 0.002; median cutpoint PD-L1: HR 2.16, p = 0.014). In multivariate analysis for OS [14 covariates included: age, race, ECOG status, anthracyclines, other chemo, endocrine, radio, other prior adjuvant therapy, disease status, ER status, PR status, Ki67 (log transformed), CK5, EGFR, serum PD-L1], elevated serum PD-L1 was a significant independent covariate [continuous PD-L1: HR 22.7, p = 0.001; median cutpoint PD-L1: HR 2.91, p = 0.0061 (Table)]. Conclusions: In the CCTG MA.31 trial, elevated pretreatment serum PD-L1was associated with a shorter OS (but not PFS) with trastuzumab treatment. Immune evasion by the tumor may decrease the effectiveness of trastuzumab therapy. Elevated serum PD-L1 may identify patients who would benefit from addition of an immune checkpoint inhibitor. Multivariate significant independent covariates for OS (186 patients). Covariate p-value Hazard Ratio Lower 95% CI Higher 95% CI Prior adjuvant/metastatic endocrine therapy (yes vs no) 0.001 4.07 1.75 9.46 Performance status (0 vs 1 or 2) 0.002 0.30 0.14 0.65 Central Review ER status (continuous IHC score) 0.006 0.99 0.98 0.99 Serum PD-L1 (pretreatment) ( > median vs < median) 0.006 2.91 1.36 6.25 Prior adjuvant / metastatic radiotherapy (yes vs no) 0.049 0.44 0.19 0.99
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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 | 0.002 | 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".