Exploration of circulating tumor cell (CTC) conversion and CTC0 as prognostic biomarkers for efficacy in TALAPRO-2: Phase 3 study of talazoparib (TALA) + enzalutamide (ENZA) vs placebo (PBO) + ENZA as first-line (1L) treatment in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC).
Bibliographic record
Abstract
5023 Background: In TALAPRO-2 (NCT03395197), pts unselected for homologous recombination repair (HRR) gene alterations received TALA + ENZA or PBO + ENZA in 1L mCRPC. TALA + ENZA significantly improved radiographic progression-free survival (rPFS) vs PBO + ENZA. In a previous analysis of five randomized phase 3 mCRPC trials, CTC reduction from ≥5 to <5 per 7.5 mL of blood (CTC conversion) or from >0 to 0 (CTC0) at a Week 13 timepoint was shown to be prognostic for overall survival, with higher discriminatory power than PSA reduction (Heller et al. J Clin Oncol. 2018;36:572-580). We examined CTC conversion and CTC0 as candidate prognostic biomarkers for rPFS in TALAPRO-2. Methods: Blood was serially collected and shipped real-time for CTC enumeration using CELLSEARCH (Menarini Silicon Biosystems) at a central laboratory (Covance). Collection timepoints were screening, Weeks 1, 9, 17, and 25, and safety follow-up visit. Baseline CTC counts were based on Week 1 (screening results were used if Week 1 results were unavailable). CTC reductions were assessed in the safety population as CTC conversion or as CTC0. Data cutoff date was August 16, 2022. Results: At baseline, 653 pts in the intent-to-treat population were evaluable for CTC counts: 213/653 (33%) had CTC counts ≥5 per 7.5 mL of blood, and 353/653 (54%) had CTC counts >0. At Week 9, 144 pts were evaluable for CTC conversion (71 TALA + ENZA, 73 PBO + ENZA), with 254 evaluable for CTC0 (119 TALA + ENZA, 135 PBO + ENZA). CTC conversion at Week 9 proved prognostic for rPFS benefit for TALA + ENZA (hazard ratio [HR]=0.13, 95% CI [0.06–0.32], 2-sided P<0.0001) and PBO + ENZA (HR=0.16 [0.07–0.40], P<0.0001). Similarly, CTC0 at Week 9 was prognostic for TALA + ENZA (HR=0.33 [0.19–0.57], P<0.0001) and PBO + ENZA (HR=0.41 [0.24–0.69], P=0.0006). At Week 17, 132 pts were evaluable for CTC conversion (64 TALA + ENZA, 68 PBO + ENZA), with 227 evaluable for CTC0 (114 TALA + ENZA, 113 PBO + ENZA). CTC conversion at Week 17 proved prognostic for rPFS benefit for TALA + ENZA (HR=0.28 [0.10–0.73], P=0.0065) and for PBO + ENZA (HR=0.26 [0.11–0.59], P=0.0006). CTC0 at Week 17 was also prognostic for TALA + ENZA (HR=0.16 [0.09–0.30], P<0.0001) and for PBO + ENZA (HR=0.36 [0.20–0.64], P=0.0004). Conclusions: CTC reduction at Week 9 and 17 proved prognostic of improved rPFS in both treatment arms in TALAPRO-2. To our knowledge, this is the first time such an association has been demonstrated in a phase 3 trial featuring a PARP inhibitor. Not all regions supported CTC collection, and missing results mainly reflected technical and logistical limitations. These results support the broad prognostic utility of CTC enumeration in mCRPC, particularly in the context of PARP inhibitor therapy. Clinical trial information: NCT03395197 .
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.001 |
| 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 | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".