Analysis of quality-adjusted time without symptoms or toxicity (Q-TWiST) in patients with metastatic hormone-sensitive prostate cancer from the ARASENS trial.

BACKGROUND

To identify patients likely to benefit from intensified darolutamide treatment while minimizing adverse events (AEs), this analysis applied quality-adjusted time without symptoms or toxicity (Q-TWiST) to evaluate quality-adjusted survival in metastatic hormone-sensitive prostate cancer in ARASENS, comparing triplet therapy (darolutamide + androgen deprivation therapy [ADT] + docetaxel) with placebo doublet therapy (ADT + docetaxel).

METHODS

Time with toxicity (TOX; with grade 3/4 symptoms/toxic effects), time without symptoms or toxicity (TWiST), and time in relapse/disease progression (REL) were estimated using 53-month restricted means based on grade 3/4 AEs, time to metastatic castration-resistant prostate cancer, and overall survival ARASENS data. Q-TWiST was calculated as the utility-weighted sum of time spent in each health state per treatment arm.

RESULTS

Patients gained an additional 6.3 months of Q-TWiST with darolutamide versus placebo (p < 0.001) driven by increased TWiST (mean 17.6 months vs 10.9 months), and decreased REL (2.4 months vs 8.7 months). Longer treatment resulted in more TOX (17.2 months vs 11.3 months) at 53 months. Partitioned Kaplan-Meier survival curves showed sustained TWiST with darolutamide versus placebo over 53 months. Relative Q-TWiST gain was 16.0% (clearly clinically important).

CONCLUSION

Darolutamide triplet therapy offers longer survival benefits without symptoms or toxicity versus placebo, aiding evaluation of efficacy-tolerability balance and supporting patient-centered decision-making.