Final results from ACIS, a randomized, placebo (PBO)-controlled double-blind phase 3 study of apalutamide (APA) and abiraterone acetate plus prednisone (AAP) versus AAP in patients (pts) with chemo-naive metastatic castration-resistant prostate cancer (mCRPC).
Bibliographic record
Abstract
9 Background: As mCRPC is driven by activated androgen receptors and elevated intratumoral androgens, androgen annihilation may require dual inhibition. APA and AA are approved prostate cancer therapies that have distinct receptor inhibition and ligand suppression actions, respectively. ACIS compared radiographic progression-free survival (rPFS) of APA + AAP vs PBO + AAP in chemo-naive mCRPC. Methods: mCRPC pts with ongoing androgen deprivation therapy (ADT) but no other life-prolonging treatment since diagnosis were randomized 1:1 to APA (240 mg po QD) + AA (1000 mg po QD) + P (5 mg po BID) or PBO + AAP (stratified by presence or absence of visceral metastases, Eastern Cooperative Oncology Group performance status 0 or 1, and geographic region). The primary end point was rPFS (investigator assessed; defined from randomization date to radiographic progression date or death). Secondary/other end points included prostate-specific antigen (PSA) response, overall survival (OS), safety, time to PSA progression, chronic opioid use, initiation of cytotoxic chemotherapy, and pain progression. Results: 982 pts were enrolled (Dec 2014 to Aug 2016). Median rPFS was extended 6 mos with APA + AAP (22.6 mos) vs AAP (16.6 mos) (HR 0.69 [95% CI 0.58-0.83]; p < 0.0001) at the final analysis for rPFS, coinciding with the first interim analysis of OS (median follow-up time 25.7 mo). At final analysis, treatment with APA + AAP vs AAP showed a significantly higher rate of confirmed ≥ 50% PSA decline. Although not statistically significant, treatment with APA + AAP vs AAP showed a longer median OS. Time to PSA progression, chronic opioid use, initiation of cytotoxic chemotherapy, and pain progression did not differ statistically significantly between arms. The safety profile was consistent with prior drug experience, with no new safety concerns. Grade 3/4 treatment-emergent adverse events (TEAEs) were reported in 63.3% (310/490) of APA + AAP–treated pts vs 56.2% (275/489) of AAP-treated pts, with more grade 3 (56.1%, 275/490 vs 45.6%, 223/489) and less grade 4 (7.1%, 35/490 vs 10.6%, 52/489) TEAEs, respectively. Results based on biomarker subpopulations and quality of life will be presented. Conclusions: The ACIS final analysis met the primary end point and demonstrated a 31% reduction in risk of radiographic progression or death in chemo-naive mCRPC pts treated with the combination of APA + AAP with ADT vs AAP with ADT. Funding: Janssen Research & Development. Trial registration: NCT02257736. Clinical trial information: NCT02257736. [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) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.002 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.015 | 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".