(UroToday.com) At the 2022 American Society of Clinical Oncology Annual Meeting held in Chicago and virtually, the oral abstract session focused on Kidney and Bladder cancers on Friday afternoon included a presentation from Dr. Robert Motzer on behalf of Dr. David Cella discussing the association between health-related quality of life metrics and clinical outcomes among patients with advanced renal cell carcinoma (RCC) treated in the context of the CheckMate-214 clinical trial.
The CheckMate 214 trial was the first to demonstrate the benefit of a combination immune checkpoint inhibitor regime in the first-line treatment of intermediate and poor-risk advanced RCC, finding both clinical benefit with improved survival outcomes and improved health related quality of life (HRQoL). In this abstract, Dr. Cella and colleagues examined the direct association between HRQoL (measured using both baseline data and longitudinal during treatment) and clinical outcomes using 5-year follow-up data. 
The design of the CheckMate 214 trial (NCT02231749) has been previously described in length – in short, this was a 1:1 randomized trial of the combination of nivolumab and ipilimumab or sunitinib among patients with advanced RCC.
Among the intermediate and poor risk subset of the cohort, 425 patients were randomized to nivolumab and ipilimumab while 422 were randomized to sunitinib. Patient-reported HRQoL was assessed using the FKSI-19 (Total Score and Disease Related Symptoms [DRS]).
In this exploratory analysis, the authors performed three separate analyses:
A: Changes in individual item scores from baseline to last assessment prior to progression were descriptively assessed.
B: For each FKSI-19 score, a multivariable Cox regression model, adjusted for treatment and stratification factors, was used to evaluate the prognostic significance of both baseline and time-dependent HRQoL scores, independently. Hazard ratios (HR) were calculated based on the risk of death per improvement in HRQoL scores, defined using the clinically meaningful change threshold (5 points for FKSI-19 Total and 3 points for DRS). Patients with overall survival (OS) events were censored if their survival event was not within 12 weeks of the last available HRQoL assessment.
C: The association between HRQoL change status (ie, improvement or maintenance vs. worsening from baseline in the FKSI-19 Total Score), irrespective of treatment arm, and OS was further assessed using a landmark analysis at the month 6 landmark. Additional landmark time points were explored in sensitivity analysis.
In this analysis, the authors considered all patients treated within the trial in aggregate, considering treatment arm as a covariate rather than stratifying characteristics. At baseline patients had somewhat lower FKSI-19 scores than a healthy sample.
The authors found that measures of the FKSI-19 relating to fatigue and perceived bother of the side-effects of treatment had the largest percentage of patients worsening prior to progression. In both baseline and time-dependent HRQoL analyses, radiographic progression-free survival was independently associated with both HRQoL measures.
This effect was even larger when the authors assessed overall survival. 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). Each 5-point increase (improvement) in FKSI-19 Total Score and 3-point increase in DRS was associated with a 31% decreased risk of death (P< 0.01).
Dr. Motzer noted that it is remarkable that longitudinal analysis is more strongly associated with survival than baseline scores. He noted that this type of analysis is novel.
At the 6-month landmark, 301 patients showed improvement or maintenance in HRQoL: these patients with improved/stable HRQoL had a 52% reduction in risk of death compared to those patients who had worsened during this time period (HR 0.48 [95% CI: 0.39-0.59]).
While the primary analysis considered the two treatment arm in aggregate, the authors also stratified patients according treatment approach. Interestingly, while there was a prognostic benefit of HRQoL response in both arms, the effect was somewhat more dramatic in patients treated with nivolumab and ipilimumab. 
The authors therefore conclude that, in the context of the CheckMate 214 trial, there is an association between HRQoL and overall survival. Thus, early changes in HRQoL may be prognostic for long term survival. Longitudinal assessment of HRQoL appears to be more strongly associated with overall survival and highlights the prognostic value of ongoing measurement of patient reported quality of life metrics.
Presented by: Robert Motzer, MD, Medical Oncologist, Memorial Sloan Kettering Cancer Center