The relationship between HRQoL and clinical outcomes in patients with advanced renal cell carcinoma in CheckMate 214

In CheckMate 214, nivolumab plus ipilimumab was associated with both clinical benefit and improved HRQoL versus sunitinib as first-line treatment for intermediate/poor-risk advanced renal cell carcinoma (aRCC) patients. Further analyses now demonstrated that baseline health-related quality of life (HRQoL) scores are a potential predictor for survival in aRCC, and HRQoL changes are informative for patients’ expected survival.

Previously, the CheckMate 214 trial demonstrated an overall survival (OS) and progression-free survival (PFS) benefit with long-term follow-up for nivolumab plus ipilimumab compared with sunitinib. In addition, nivolumab plus ipilimumab showed health-related quality of life (HRQoL) benefits versus sunitinib. Prior studies could show an association between HRQoL and efficacy outcomes in renal cell carcinoma (RCC) and other malignancies. Cella et al. explored the prognostic ability of HRQoL data to help inform on risk of progression or death in patients with advanced RCC (aRCC).

Study Design

This analysis used five-year follow-up data of intermediate/poor-risk aRCC patients from the CheckMate 214 study to assess the following associations: baseline HRQoL and PFS, baseline HRQoL and OS, longitudinal HRQoL and PFS, and longitudinal HRQoL and OS. In this, baseline HRQoL refers to data collected pre-treatment at randomisation while longitudinal HRQoL refers to HRQoL data collected after randomisation while on study and afterwards. HRQoL was assessed using the Functional Assessment of Cancer Therapy Kidney Symptom Index (FKSI-19) total score and disease-related symptoms-physical (DRS-P) subscale.

In CheckMate 214, HRQoL was an exploratory endpoint and included the FKSI-19 instrument. Two different Cox proportional hazard models were fitted to time-to-event data: baseline HRQoL scores (i.e. time-invariant) and longitudinal HRQoL scores (i.e. time-dependent). Treatment arm, IMDC prognostic score and geographic region were included as covariates along with the HRQoL scores. The hazard ratio (HR) for the HRQoL variable was the key measure, calculated as the hazard (risk) of progression or death per improvement in HRQoL scores. Improvement was defined using 5 points for FKSI-19 total score and 4 points for DRS-P.

Results

In total, 847 IMDC intermediate- and poor-risk patients from both arms of the CheckMate 214 trial were included in the analysis. Completion rates of patient-reported outcomes (PRO) questionnaires were high at baseline (≥95%) and remained high for the duration of the study (≥75% for all visits except one using 5-year follow-up data).

The association between better baseline scores and longer PFS is indicated by a hazard ratio and 95% confidence interval being below 1. For the longitudinal model, an improved score over the course of treatment was associated with lower risk of progression or death. In both baseline and time-dependent HRQoL analyses, OS was independently associated with both HRQoL measures. Higher (better) baseline scores were associated with significantly reduced risk of death (HR [95% CI] for FKSI-19 Total Score and DRS was 0.83 [0.80-0.87] and 0.80 [0.76-0.84], respectively). In the longitudinal model, every 5-point increase (improvement) in FKSI-19 Total Score was associated with a 31% decreased risk of death while every 4-point improvement in DRS-P score was associated with a 35% reduction in the risk of death. These results suggest a stronger association between longitudinal HRQoL scores and OS, compared with baseline HRQoL only and OS. At six months, 301 patients showed improvement or maintenance in HRQoL. Patients with improved or stable HRQoL had a 52% reduction in risk of death compared to patients who had worsened (HR[95%CI]: 0.48[0.39-0.59], p< 0.0001), with mOS of 67.8 months for HRQoL responders and only 32.0 months for HRQoL non-responders. Similar results were observed for the DRS-P score. The landmark analysis at six months was also performed for each of the CheckMate 214 arms separately. OS benefits were observed for patients on each treatment arm for HRQoL responders vs. non-responders.

Conclusion

Better HRQoL scores were associated with a longer PFS and OS in intermediate/poor-risk RCC patients treated in the CheckMate 214 trial. A stronger association was suggested for longitudinal HRQoL and OS, compared with the baseline HRQoL model. These results highlight the value of PRO in measuring patients’ HRQoL and for prognostic modelling.

Reference

Cella D, et al. The relationship between health-related quality of life (HRQoL) and clinical outcomes in patients with advanced renal cell carcinoma (aRCC) in CheckMate (CM) 214. Presented at ASCO 2022; Abstract 4502.