Impact of on-study corticosteroid use on efficacy and safety in the phase III AFFIRM study of enzalutamide (ENZA), an androgen receptor inhibitor.
Bibliographic record
Abstract
6 Background: ENZA increased median overall survival (OS) by 4.8 mo (P <0.001, HR 0.63) vs placebo (PBO) in metastatic castration-resistant prostate cancer (mCRPC) patients (pts) post-docetaxel in AFFIRM (HI Scher et al, NEJM 2012). Corticosteroids (CS) can activate AR signaling in nonclinical models (J Richards, Can Res 2012). In a multivariate model of AFFIRM data baseline CS use was associated with reduced OS (HI Scher et al. ESMO 2012 abstract 899PD). The impact of CS use during study treatment in AFFIRM was evaluated to test if concomitant CS use is also associated with inferior outcomes. Methods: Pts were randomized 2:1 to ENZA 160 mg/d or PBO. Pts were allowed but not required to take CS. OS was the primary endpoint. In a post-hoc analysis On-study CS use was defined as oral CS user for ≥ 1 day on study. Results: On study CS use was 48% in ENZA and 45% in PBO pts. Prognostic factors were slightly better in the no CS group compared to the CS group. Use of CS regardless of treatment was associated median OS of 11.5 mo (95% CI: 10.5, 13.0) for CS pts vs median OS NM (NM, NM) for no CS pts (HR=0.40; 95% CI: 0.33, 0.48). ENZA was consistently superior to PBO for OS, radiographic progression free survival (rPFS) and time to PSA progression (TTPP), regardless of CS use (Table). Pts on CS had higher rates of grade 3 - 4 adverse events (AE) compared to no CS pts: 63.3% vs 34.4% respectively. Conclusions: In this post-hoc analysis, on study CS use was associated with reduced OS and higher rates of grade 3 -4 AEs in mCRPC pts post-docetaxel. While CS pts had worse outcomes, ENZA was consistently superior to PBO regardless of on study CS use. The inferior outcomes in CS pts may be due to unmeasured confounders or the biologic properties of CS use itself. Clinical trial information: NCT00974311. [Table: see text]
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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 | 0.003 | 0.003 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 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 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".