The menopause after cancer study (MACS) - A multimodal technology assisted intervention for the management of menopausal symptoms after cancer

Background: Vasomotor symptoms (VMS) of menopause represent a significant challenge for many patients after cancer treatment, particularly those for whom conventional menopausal hormone therapy (MHT) is contraindicated. There is currently no gold standard of treatment in this cohort. Methods: The Menopause after Cancer (MAC) Study (NCT04766229) was a single arm phase II trial examining the impact of a composite intervention on quality of life (QoL) in women with moderate to severe VMS after cancer. The intervention consisted of: (1) use of non-hormonal pharmacotherapy to manage VMS (citalopram for predominantly daytime VMS and/or gabapentin for predominantly nocturnal VMS) (2) digital cognitive behavioural therapy for insomnia (dCBT-I) using Sleepio (BigHealth), (3) self-management strategies for VMS delivered via a mobile application called myPatientSpace and (4) nomination of an additional support person/partner. The primary outcome was cancer specific global QoL assessed by the EORTC QLC C-30 version 3 at 6 months. Secondary outcomes included frequency of VMS, bother/interference of VMS (hot flush rating scale [HFRS]) and prevalence of insomnia (sleep condition indicator [SCI] ≥16) at 6 months. Results: 204 women (82% history of breast cancer) with a median age of 49 years (range 28-66) were recruited. Participants had a mean of 11.8 hot flashes in a day (SD9.2) and 5.1 night sweats each night (SD4.9). 17.1% of participants were prescribed citalopram, 62.8% were prescribed gabapentin alone and 20.1% were prescribed both medications. 120 women completed the protocol. Frequency of VMS decreased by 50% at 6 months. In the intention to treat (ITT) cohort (n=204) baseline global QoL scores increased from 62.2 (95%CI 58.58-65.44) to 70.4 (95%CI 67.08-73.77) at 6 months (p<0.001). In the per protocol (PP) cohort, (n=120) baseline QoL scores increased from 62 (95%CI 58.58-65.44) to 70.4 (67.08-73.77) at 6 months (p<0.001). Clinically meaningful improvements were also seen in cognitive function, emotional function, role function and social functioning in both ITT and PP cohorts at 6 months. Bother/interference of VMS decreased, the baseline HFRS score of 7.6 (95%CI 7.37-7.74) decreased to 3.4 (95%CI 2.98-3.75) at 6 months (p<0.001) in the ITT cohort (7.5 (95%CI 7.30-7.77) to 3.4 (2.98-3.74) at 6 months (p=0.036) in the PP cohort). The prevalence of insomnia reduced from 93.1% at baseline to 45.2% at 6 months (p<0.001) with SCI scores increasing from a baseline of 8.5 (SEM 0.4) to 17.3 (SEM 0.5) at 6 months (p<0.0005) in the ITT cohort ( 7.9 (SEM 0.4) to 17.3 (SEM 0.5) at 6 months (p<0.001) in the PP cohort) indicating significant improvement in insomnia symptoms. Wakefulness after sleep onset and sleep onset latency also decreased during the trial in both cohorts. Conclusion: The MAC study demonstrates that improvements in quality of life can be achieved using this multimodal intervention to target VMS and insomnia after cancer.