Impact of baseline hot flashes on sleep metrics during initial treatment in LIBERTAS clinical trial.

Abstract

186 Background: Libertas is a study of intermittent ADT administered with apalutamide monotherapy in metastatic castration sensitive prostate cancer. Sleep disturbances are prevalent among these patients and can substantially impair quality of life and influence therapeutic efficacy. Vasomotor symptoms, particularly hot flashes, are frequently reported during hormonal therapy and may exacerbate sleep disruption. Understanding the association between hot flashes and sleep metrics is essential for optimizing supportive care strategies and enhancing overall treatment outcomes in this population. Methods: Participants were stratified into two groups based on severity-adjusted hot flash scores: No Hot Flash (score = 0) and Any Hot Flash (score > 0). Digital sleep metrics-Wake After Sleep Onset (WASO), number of awakenings, and sleep efficiency-were derived from triaxial acceleration data collected via the Ametris CentrePoint Insight Watch, that participants wore on wrist throughout the study. Sleep/wake classification was performed using validated algorithms (Cole-Kripke or Sadeh). Sleep metrics were aggregated over ±7-day window around the time point of hot flash diary collection. Wilcoxon rank-sum test was used to assess statistically significant differences in sleep metrics between groups at each timepoint. Actigraphy compliance ranged between 90.49% – 92.62% across timepoints, calculated as the percentage of time the device was worn over a 24-hour period. In addition, sleep disturbances and fatigue were also evaluated using the PHQ-9 questionnaire, offering patient-reported insights into overall well-being. Results: Following the start of initial treatment phase, all participants showed increased WASO, number of awakenings and a decline in sleep efficiency. PHQ-9 data also indicated heightened sleep disturbances and fatigue, despite stable depression scores during initial treatment phase. Participants with baseline hot flashes experienced a statistically significant greater increase in WASO and number of awakenings, and a statistically significant lower decline in sleep efficiency compared to those without baseline hot flashes (p<0.05). By the end of the initial phase, both groups trended toward baseline values; however, the baseline hot flash group maintained statistically significant higher WASO and lower sleep efficiency (p < 0.05). Furthermore, individual PHQ-9 items revealed a similar pattern of sleep disturbance, highlighting subjective experiences aligned with objective sleep metrics. Conclusions: Baseline hot flashes were associated with more pronounced and enduring sleep disturbances during the initial treatment phase in participants with prostate cancer. These findings emphasize the critical need for simultaneous monitoring of vasomotor symptoms and sleep quality, and may inform targeted interventions to improve patient well-being during therapy. Clinical trial information: NCT05884398 .