| Abstract: |
Background: For patients with advanced renal cell carcinoma, maintaining quality of life during treatment is a priority. The phase III CheckMate 9ER study demonstrated improved efficacy and health-related quality of life (HRQoL) outcomes with first-line cabozantinib plus nivolumab (CaboNivo) versus sunitinib (Sun) and underscored the need to improve understanding of the relationship between clinical efficacy and the patient treatment experience. In this work, we investigated the relationship between changes in HRQoL and clinical outcomes, as well as identifying symptom-based patient profiles that could predict disease course and clinical outcomes. Materials and methods: This post hoc analysis of CheckMate 9ER used the patient-reported outcomes 19-item Functional Assessment of Cancer Therapy—Kidney Symptom Index (FKSI-19) to evaluate HRQoL. Cox proportional modeling was used to investigate the association between early changes in FKSI-19 scores and clinical outcomes, while latent class analysis (LCA) was used to identify symptom-based patient profiles. Results: The nature of patient-reported symptoms was similar at baseline and 13 weeks for CaboNivo and Sun, but symptom frequency varied between arms. Early worsening of bone pain [hazard ratio (HR) 1.45, P = 0.010] and sleep quality (HR 1.45, P = 0.007) were associated with increased risk of mortality. The LCA identified three distinct subgroups of patients by symptom burden and risk profile. Patients in the limited symptoms class at week 13 were more likely to have received CaboNivo (limited: 63.4%; moderate-to-severe: 45.9%; severe: 38.5%), had a longer duration of treatment (>122 weeks: 37.2% versus 14.7% versus 17.9%), and were generally less likely to experience disease progression (61.6% versus 55.1% versus 76.9%) than other symptom classes. Conclusions: This post hoc analysis identified an association between efficacy and HRQoL based on data from CheckMate 9ER. These results highlight the necessity of balancing treatment choice, tolerability, and HRQoL to optimize treatment outcomes and support shared decision-making. © 2025 The Authors |
