Concurrent chemo-hormonal therapy of enzalutamide (ENZ) and cabazitaxel (CAB) in patients (Pts) with metastatic castration-resistant prostate cancer (mCRPC): Final analysis of objective response rate (ORR), radiographic progression-free survival (rPFS), and overall survival (OS).
Bibliographic record
Abstract
5047 Background: We previously reported the PSA response rate and toxicity data of a phase 1/2 single-arm, multi-institutional trial to examine the efficacy and safety of co-administration of ENZ + CAB in mCRPC without prior chemotherapy given in the mCRPC setting. We found that full doses of ENZ (160 mg daily) and CAB (25 mg/m2) were tolerable and that 80% of pts had PSA decline ≥50%. Here, we report the final analysis of ORR, rPFS and OS. Methods: We calculated the ORR (CR/PR) and 95% confidence intervals using the Clopper-Pearson Exact Method. We determined response according to RECIST 1.1 for measurable disease and Prostate Cancer Working Group 2 criteria for non-measurable (bone) disease. We estimated median rPFS (time from the study entry to the time of confirmed progression (radiographic or clinical) or death) and OS (time from the study entry to death) with 95% confidence intervals using the Kaplan-Meier method; data cutoff was 6/1/22. Statistical analysis was performed using R: A language and environment for statistical computing. Results: 37 pts consented and 35 were included in the efficacy analyses (1 withdrew consent, 1 was lost to follow up before efficacy assessment); 7/35 (20%) had prior exposure to chemotherapy given for mHSPC and 9/35 (25%) had prior exposure to abiraterone (ABI), including 2/35 (25.7%) with prior exposure to chemotherapy and ABI. 28 pts had at least one on-study trial imaging study and were evaluable for ORR. After a median follow-up of 23.7 (range: 4.9 to 62.4) months (mo), median OS was 25.1 mo (95%CI 19.4 - 37.6 mo). Median PSA PFS was 11.9 mo (95%CI 9.2 - 15.4), and median rPFS was 22.2 mo (95%CI 13.6 - 25.2). PK assessments revealed that ENZ decreased CAB levels: CAB (monotherapy) Cmax 178.9ng*h/ml vs CAB (in the presence of ENZ) Cmax 85.5 ng*h/ml (p<0.05). Conclusions: The combination of ENZ+CAB in this heterogeneous mCRPC population, which included about a quarter of pts with prior chemotherapy and ABI exposure, resulted in an OS of 22.5 mo comparing favorably with the OS of 25.2 mo seen in the FIRSTANA trial of single agent CAB in docetaxel naïve men, 15.1 mo post chemotherapy in the TROPIC trial, and 13.6 mo in the post-docetaxel, post-ABI in the CARD trial. Of note, the rPFS in this trial was 22.2 months compared to 5.1 months in FIRSTANA suggesting improved efficacy; however cross-trial comparisons are discouraged due to several confounders. Chemo-hormonal therapies and prognostic/predictive biomarkers warrant further study in mCRPC. Clinical trial information: NCT02522715 . [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 | 0.002 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".