Talazoparib (TALA) plus enzalutamide (ENZA) in metastatic castration-resistant prostate cancer (mCRPC): Safety analyses from the randomized, placebo (PBO)-controlled, phase 3 TALAPRO-2 study.
Bibliographic record
Abstract
5053 Background: The phase 3 TALAPRO-2 study demonstrated a clinically meaningful and statistically significant improvement in radiographic progression-free survival for 1st-line TALA + ENZA versus PBO + ENZA in men with mCRPC, unselected for homologous recombination repair gene alterations (all-comers population). Here, we detail the safety profile of TALA + ENZA. Methods: In this double-blind, randomized, PBO-controlled trial, men received TALA 0.5 mg or PBO, plus ENZA 160 mg once daily (QD). Patient (pts) were ≥18 yrs of age, had Eastern Cooperative Oncology Group performance status ≤1, were receiving ongoing androgen deprivation therapy, and had no prior systemic therapy for mCRPC. Treatment-emergent adverse events (TEAEs) were evaluated: type, severity, timing, and associated dose modifications/discontinuations. Results: The all-comers safety population included 398 pts in the TALA + ENZA arm. Data cutoff was August 16, 2022. The median treatment duration of TALA was 19.8 months. All-cause any-grade TEAEs were observed in 98.5% of pts. Overall, 19.1% of pts discontinued TALA due to TEAEs. The 3 most common hematologic all-cause TEAEs and associated dose modifications are reported. To ensure optimal dosing of TALA at the individual level, the protocol did not require dose modification of TALA until anemia was grade (G) ≥3. Median time to onset of first G≥3 anemia was 3.3 months. At study entry, 49.0% had G1–2 anemia. 43.2% had anemia leading to dose reduction (with or without transfusion) and 8.3% discontinued TALA due to anemia. Despite dose reduction, the relative dose intensity of talazoparib remained >80% (approx. 0.4 mg/day). The 3 most common nonhematologic TEAEs were fatigue (33.7%; 4.0% G3), back pain (22.1%; 2.5% G3), and decreased appetite (21.6%; 1.3% G3). Conclusions: TALA 0.5 mg QD + ENZA 160 mg QD was generally manageable, with dose modifications of TALA and/or standard supportive care. Anemia was the most common TEAE and led to discontinuation of TALA in 8.3% of pts. G≥3 hematologic AEs typically occurred within 6 months of starting therapy and resolved in <1 month. A detailed understanding of the onset, duration, and severity of AEs, as well as the impact of dose adjustments in the TALAPRO-2 study, will optimize the management of pts receiving TALA + ENZA for mCRPC. Clinical trial information: NCT03395197 . [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 | 0.001 | 0.001 |
| 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 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".