Olaparib plus Abiraterone for Metastatic Castration-resistant Prostate Cancer: Pharmacokinetics Data from the PROpel Trial
Bibliographic record
Abstract
PROpel (NCT03732820) was a positive phase 3 trial that demonstrated a clinically significant improvement in radiographic progression-free survival with olaparib plus abiraterone versus placebo plus abiraterone in first-line metastatic castration-resistant prostate cancer. For a subset of PROpel patients, steady-state concentrations of olaparib, abiraterone, and Δ4-abiraterone were measured in blood samples collected before and at several time points after dose administration. The pharmacokinetics (PK) for each drug and metabolite were evaluated to determine whether any clinically relevant drug-drug interactions between olaparib and abiraterone occurred. The results demonstrate that steady-state PK parameters for olaparib and abiraterone in PROpel were comparable with those in monotherapy trials. Abiraterone steady-state exposures were similar between treatment arms. Δ4-Abiraterone had slightly lower steady-state exposures when abiraterone was administered in combination with olaparib. These results are consistent with a previous phase 2 study, supporting the conclusion that no clinically relevant PK-based drug-drug interactions occurred when olaparib and abiraterone were given in combination at their full monotherapy doses.Patient summaryWhen drugs are administered in combination, a key consideration is whether there are any interactions between the drugs that may affect their activity. We analyzed blood concentrations of olaparib and abiraterone in a subset of patients with prostate cancer from the PROpel trial to determine if there were interactions between these two drugs. We found that there was no significant effect on the profile of either drug when they were given together at the same doses used when each drug is given individually.
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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 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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".