In an analysis from the phase III CheckMate 9ER trial reported in The Lancet Oncology, David Cella, PhD, FASCO, and colleagues found that nivolumab/cabozantinib was associated with maintained or improved patient-reported outcomes vs sunitinib in the first-line treatment of advanced renal cell carcinoma. In the trial, nivolumab/cabozantinib significantly improved progression-free survival vs sunitinib.
David Cella, PhD, FASCO
Study Details
In the open-label trial, 651 patients from sites in 18 countries were randomly assigned between September 2017 and May 2019 to receive nivolumab at 240 mg every 2 weeks plus cabozantinib at 40 mg per day (n = 323) or sunitinib at 50 mg per day for 4 weeks on/2 weeks off. Patient-reported outcomes were analyzed as prespecified exploratory endpoints at baseline and every 6 weeks until week 115.
Patient-reported outcome assessments included the Functional Assessment of Cancer Therapy-Kidney Symptom Index (FKSI-19) total score (range = 0–76), FKSI-19 disease-related symptoms version 1 score (range = 0–36), EQ-5D-3L visual analog scale (VAS; range = 0–100) and UK utility index (range = 0–1); for all scales, higher scores indicate better status. Analyses were performed in the intent-to-treat population.
Key Findings
Median follow-up was 23.5 months (interquartile range = 21.0–26.5 months). At baseline, mean FKSI-19 total scores were 58.74 in the nivolumab/cabozantinib group and 58.39 in the sunitinib group. Both groups had low symptom burden, as indicated by mean FKSI-19 disease-related symptoms version 1 scores of 30.24 and 30.06 at baseline.
Between-group changes from baseline favored nivolumab/cabozantinib for:
- FKSI-19 total score (treatment difference = 2.38, 95% confidence interval [CI] = 1.20–3.56, nominal P < .0001; effect size = 0.33, 95% CI = 0.17–0.50)
- FKSI-19 disease-related symptoms version 1 (treatment difference = 1.33, 95% CI = 0.84–1.83, nominal P < .0001; effect size = 0.45, 95% CI = 0.28–0.61)
- EQ-5D-3L VAS (treatment difference = 3.48, 95% CI = 1.58–5.39, nominal P = .0004; effect size = 0.30, 95% CI = 0.14–0.47)
- EQ-5D-3L UK utility index (treatment difference = 0.04, 95% CI = 0.01–0.07, nominal P = .0036; effect size = 0.25, 95% CI = 0.08–0.41).
The differences between nivolumab/cabozantinib and sunitinib in these measures were significant at most time points.
In time-to-deterioration analysis, nivolumab/cabozantinib was associated with significantly prolonged time to clinically meaningful deterioration on FKSI-19 total score vs sunitinib. Median time to first deterioration event (random assignment to first date a patient had a change from baseline meeting or exceeding the prespecified primary meaningful change threshold for the scale) was 6.24 months vs 3.48 months (hazard ratio [HR] = 0.70, 95% CI = 0.56–0.86, nominal P = .0007). Median time to confirmed deterioration event (event either confirmed at the next consecutive scheduled visit or followed by dropout) was 19.38 months vs 6.97 months (HR = 0.63, 95% CI = 0.50–0.80, nominal P = .0001). Findings were similar for the FKSI-19 disease-related symptoms version 1 scale.
The investigators concluded, “Patient-reported outcomes were maintained or improved with nivolumab plus cabozantinib vs sunitinib. Compared with sunitinib, nivolumab plus cabozantinib significantly delayed time to deterioration of patient-reported outcome scores. These results suggest a benefit for nivolumab plus cabozantinib compared with sunitinib in the treatment of patients with advanced renal cell carcinoma.”
Dr. Cella, of the Robert H. Lurie Comprehensive Cancer Center, Northwestern University, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by Bristol Myers Squibb. For full disclosures of the study authors, visit thelancet.com.
