Olaparib combined with abiraterone in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC): A randomized phase II trial.
Bibliographic record
Abstract
5003 Background: mCRPC pts with a homologous recombination repair mutation (HRRm) previously showed improved response to the PARP inhibitor olaparib (Lynparza) as monotherapy vs pts without a HRRm (Mateo J et al, NEJM 2015). We report data from a Phase II, placebo-controlled trial of olaparib combined with the anti-hormonal therapy abiraterone in post-chemotherapy mCRPC pts whose tumors did not need to have a HRRm (NCT01972217). Methods: mCRPC pts were randomized (1:1) post-docetaxel to olaparib 300 mg bid (tablets; combination) or placebo (comparator) plus abiraterone (1000 mg od) and treated until disease progression. Primary endpoint was investigator-assessed radiologic progression-free survival (rPFS; RECIST 1.1, PCWG-2). HRRm status was assessed using optional tumor (n = 68), whole-blood and plasma samples. Results: 142 pts (median age: 69 yrs) were randomized and treated (both arms, n = 71). Overall, a statistically significant increase in rPFS was seen with the combination vs comparator (Table; P= 0.03). A rPFS benefit in the combination arm was suggested irrespective of HRRm status. Median overall survival was 23.3 vs 20.9 mths in the combination vs comparator arms, respectively (HR 0.89, 95% CI 0.58–1.35). 54% vs 28% of pts, respectively, had grade ≥3 AEs; 34% vs 18% reported serious AEs, including more cardiovascular AEs with the combination. 30% vs 10% of pts, respectively, discontinued treatment due to an AE. Median time to deterioration in quality of life (QoL; FACT-P) was 5.7 vs 6.0 mths, respectively (HR 0.97, 95% CI 0.68–1.40). Conclusions: This is the first trial to show clinical benefit for mCRPC pts treated with a PARP inhibitor combined with abiraterone, regardless of HRRm status. Safety data were less favorable for the combination, but no detriment to QoL was seen. Our study indicates synergy between olaparib and abiraterone. Clinical trial information: NCT01972217.rPFS by HRRm status. Pt group Median rPFS,* mths (combination vs comparator) HR (95% CI) Overall, n = 142 13.8 vs 8.2 0.65 (0.44–0.97) HRRm, n = 21 17.8 vs 6.5 0.74 (0.26–2.12) HRRwt,† n = 35 15.0 vs 9.7 0.52 (0.24–1.15) HRRm unknown, n = 86 13.1 vs 6.4 0.67 (0.40–1.13) *Kaplan-Meier method; †tumor test result required. wt, wild-type.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.007 | 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".