SRS135 - Assessing the impact of advancements in human epidermal growth factor receptor-2-positive breast cancer therapeutics on quality of life: a systematic review and meta-analysis of randomised controlled trials

Abstract Background Targeted molecular therapy has transformed the management of human epidermal growth factor receptor-2 (HER2+) breast cancer. Alongside survival outcomes, randomised controlled trials (RCTs) are increasingly incorporating quality of life (QoL) and patient-reported outcome measures (PROMs). Aim To systematically evaluate how RCTs of targeted therapies in breast cancer have assessed PROMs and QoL, and to investigate whether treatment effects on overall survival (OS) and progression-free survival (PFS) align with preservation of QoL. Methods A systematic review and meta-analysis was conducted in accordance with PRISMA guidelines. Statistical analyses were performed using R. Results Twenty-five RCTs involving 24 234 HER2+ breast cancer patients (mean age 55.6 years, range 20–91) were included. CONSORT-PRO scores ranged from 5–9 (median 8.0). Meta-analysis demonstrated that antibody-drug conjugates (ADCs) significantly prolonged time to deterioration compared with non-ADC therapies in the metastatic setting (HR 0.64, 95% c.i. 0.49–0.83; P < 0.0001) and were associated with an improvement in QoL change from baseline (MD = 2.0 points, 95% c.i. 0.4–3.6; P = 0.015). Dual HER2 blockade significantly prolonged time to deterioration (TTD) (HR 0.81, 95% c.i. 0.69–0.94; P = 0.006). Trial-level associations between TTD and OS (P = 0.73) and between TTD and PFS (P = 0.91) were not significant. Conclusions Breast cancer RCTs increasingly integrate PROMs, reflecting a shift towards patient-centred evaluation. While treatments significantly prolonged TTD, there was no consistent evidence that survival gains translated into better QoL preservation. These findings highlight the need for future trials to balance efficacy with sustained quality of life.