Impact of adjuvant systemic cancer therapies on health-related quality of life: A systematic review of randomized controlled trials.

Abstract

e23200 Background: Adjuvant systemic treatments reduce the risk of cancer recurrence and can improve survival in various cancer types. However, adverse events (AE) caused by these therapies could potentially negatively impact patients' health-related quality of life (HRQoL). New symptoms can be reliably attributed to treatment rather than the underlying cancer in the adjuvant setting. Patient-reported outcomes (PRO) have become more widely implemented in randomized controlled trials (RCT). We sought to explore the impact of adjuvant systemic cancer therapies on HRQoL in adjuvant cancer therapy RCTs across all tumor types. Methods: We searched PubMed and Embase (1980-November 2023) for RCTs that reported HRQoL data and compared adjuvant systemic cancer therapies (experimental arm) to placebo or observation (control arm) after curative local cancer treatment. Our search and data collection focused on reviewing the impact of different adjuvant systemic cancer modalities on the HRQoL of various cancer patients. Results: Our study identified 33 trials meeting our criteria, 25 of which (75.8%) concluded that adjuvant therapy showed no clinically significant change in HRQoL compared to the placebo or observation. In contrast, the treatment arm in all evaluable studies had significantly higher rates of grade 3+ AEs, serious adverse events (SAEs), and treatment discontinuation (due to side effects) than the control arm. The most common cancer types were melanoma (30.3%), genitourinary (21.2%), breast (15.2%), and gastrointestinal (15.2%). Immunotherapy (36.4%), targeted therapy (27.2%), and chemotherapy (21.2%) were the predominant adjuvant systemic treatments (Table 1). Double-blinded studies rarely (11.1%) reported clinically significant changes in overall HRQoL in the experiment arm, while open-label studies more frequently (42.9%) reported CSC. Conclusions: Despite higher adverse event rates, most published RCTs reported no clinically significant impact of adjuvant systemic therapies on overall HRQoL compared to placebo or observation. This inconsistency may stem from low PRO specificity, insensitive measures, publication bias, response shift, and arbitrary minimal clinically important difference (MCID) thresholds. Minimal HRQoL impact does not indicate well-tolerated treatment. Further investigation is needed on PRO assessment efficiency and the relationship between AEs and HRQoL. Results stratified by therapy modality. Therapy Modality CSC n (%) NCSC n (%) Total (n) Targeted Therapy 1 (3.0) 8 (24.2) 9 Chemotherapy 2 (6.1) 5 (15.2) 7 Hormonal Therapy 0 (0.0) 4 (12.1) 4 Immune Checkpoint Inhibitor 0 (0.0) 6 (18.2) 6 Interferon 3 (9.1) 1 (3.0) 4 Chemotherapy and Immunotherapy 1 (3.0) 0 (0.0) 1 Other types of Immunotherapies 1 (3.0) 1 (3.0) 2 CSC: Clinically Significant Change; NCSC: No Clinically Significant Change.