In a study reported in The Lancet Oncology, Robert Motzer, MD, and colleagues found that patients with previously untreated advanced renal cell carcinoma receiving lenvatinib/pembrolizumab had similar or favorable health-related quality of life scores and prolonged time to definitive deterioration vs those receiving sunitinib.
As noted by the investigators, the phase III CLEAR trial, which compared lenvatinib plus either pembrolizumab or everolimus vs sunitinib, showed that lenvatinib/pembrolizumab improved progression-free and overall survival compared with sunitinib. The current health-related quality-of-life analysis thus included comparison between the lenvatinib/pembrolizumab vs sunitinib groups.
Study Details
In the open-label trial, patients were randomly assigned 1:1:1 to receive lenvatinib at 20 mg per day plus pembrolizumab at 200 mg every 21 days (n = 355), lenvatinib at 18 mg per day plus everolimus at 5 mg per day (n = 357) in 21-day cycles, or sunitinib at 50 mg per day 4 weeks on followed by 2 weeks off (n = 357). In the current analysis, health-related quality of life in the lenvatinib/pembrolizumab group and sunitinib group were evaluated by the Functional Assessment of Cancer Therapy Kidney Symptom Index-Disease-Related Symptoms (FKSI-DRS), EORTC QLQ-C30, and EQ-5D-3 Level questionnaire at baseline and on day 1 of each subsequent 21-day cycle. Scores were transformed to 0 to 100 scales; for the EORTC QLQ-C30 global health status/quality of life (GHS/QOL) and functional scales, a higher score corresponds to better health-related quality of life, whereas for symptom scales, a higher score represents worsening of symptoms.
Deterioration events were defined as detrimental changes in score relative to baseline that exceeded the minimally important difference thresholds for the individual scales. Definitive deterioration was defined as the earliest deterioration event during the treatment period with no subsequent recovery above the deterioration threshold or no subsequent health-related quality-of-life assessment data.
These [health-related quality-of-life] results demonstrate that patients given lenvatinib plus pembrolizumab treatment had similar or favorable scores compared with patients given sunitinib, particularly with respect to time to definitive deterioration. These results support the efficacy and safety profile of lenvatinib plus pembrolizumab as first-line therapy for patients with advanced renal cell carcinoma.— Robert Motzer, MD
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Key Findings
Median follow-up for health-related quality-of-life analyses was 12.9 months (interquartile range = 5.6–22.3 months).
Least squares mean changes (standard error) from baseline in the lenvatinib/pembrolizumab group vs the sunitinib group were –1.75 (0.59) vs –2.19 (0.66) for FKSI-DRS, –5.93 (0.86) vs –6.73 (0.94) for EORTC QLQ-C30 GHS/QOL, and –4.96 (0.85) vs –6.64 (0.94) for the EQ-5D visual analoge scale. The lenvatinib/pembrolizumab group was nominally significantly favored vs the sunitinib group on four EORTC QLQ-C30 scales (physical functioning, fatigue, dyspnea, and constipation), but not for any other scales. The sunitinib group was not favored vs the lenvatinib/pembrolizumab group on any scale.
Median time to first deterioration in the lenvatinib/pembrolizumab group vs the sunitinib group was 9.14 weeks (95% confidence interval [CI] = 6.43–12.14 weeks) vs 12.14 weeks (95% CI = 9.14–15.29 weeks; hazard ratio [HR] = 1.13, 95% CI = 0.94–1.35, P = .20) on the FKSI-DRS, 12.00 weeks (95% CI = 7.29–15.14 weeks) vs 9.14 weeks (95% CI = 6.29–12.14 weeks; HR = 0.88, 95% CI = 0.74–1.05, P = .17) on the EORTC QLQ-C30 GHS/QOL, and 9.43 weeks (95% CI = 6.43–12.29 weeks) vs 9.14 weeks (95% CI = 6.29–12.00 weeks; HR = 0.83, 95% CI = 0.70–0.99, P = .041) on the EQ-5D visual analog scale.
Median time to definitive deterioration in the lenvatinib/pembrolizumab group vs the sunitinib group was 134.14 weeks (95% CI = 120.00 weeks–not estimable) vs 117.43 weeks (95% CI = 90.14–131.29 weeks; HR = 0.70, 95% CI = 0.53–0.92, P = .0081) on the FKSI-DRS, 114.29 weeks (95% CI = 102.14–153.29 weeks) vs 75.14 weeks (95% CI = 57.29–105.14 weeks; HR = 0.60, 95% CI = 0.47–0.77, P < .0001) on the EORTC QLQ-C30 GHS/QOL, and 124.86 weeks (95% CI = 94.71–134.57 weeks) vs 74.86 weeks (95% CI = 54.14–96.00 weeks; HR = 0.67, 95% CI = 0.53–0.85, P = .0012) on the EQ-5D visual analog scale.
The investigators concluded, “These [health-related quality-of-life] results demonstrate that patients given lenvatinib plus pembrolizumab treatment had similar or favorable scores compared with patients given sunitinib, particularly with respect to time to definitive deterioration. These results support the efficacy and safety profile of lenvatinib plus pembrolizumab as first-line therapy for patients with advanced renal cell carcinoma.”
Dr. Motzer, of Memorial Sloan Kettering Cancer Center, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by Eisai and Merck Sharp & Dohme, a subsidiary of Merck & Co. For full disclosures of the study authors, visit thelancet.com.
