Health-related quality-of-life outcomes in patients with advanced renal cell carcinoma treated with lenvatinib plus pembrolizumab or everolimus versus sunitinib (CLEAR): a randomised, phase 3 study
Mené dans 20 pays sur 355 patients atteints d'un carcinome à cellules rénales de stade avancé (durée médiane de suivi : 12,9 mois), cet essai de phase III compare l'intérêt, du point de vue de la qualité de vie, d'un traitement de première ligne combinant lenvatinib et pembrolizumab ou évérolimus, et du sunitinib en monothérapie
Background : Results from the phase 3 CLEAR study showed that lenvatinib plus pembrolizumab improved progression-free survival and overall survival compared with sunitinib in patientswith advanced renal cell carcinoma. We aimed to assess the health-related quality-of-life(HRQOL) outcomes from the CLEAR study. Methods : This open-label, randomised, phase 3 study was done across 200 hospitals and cancercentres in 20 countries. Patients were required to be 18 years or older, with advancedclear-cell renal cell carcinoma, and a Karnofsky performance status of 70% or higher.Patients who had received previous systemic anticancer therapy for renal cell carcinomawere not eligible. Patients were randomly assigned (1:1:1) to lenvatinib (oral 20mg per day) plus pembrolizumab (intravenous 200 mg every 21 days), lenvatinib (oral18 mg per day) plus everolimus (oral 5 mg per day) in 21-day cycles, or sunitinib(oral 50 mg per day, 4 weeks on followed by 2 weeks off). Patients were assigned totreatments with a computer-generated randomisation scheme and were stratified by geographicalregion and Memorial Sloan Kettering Cancer Center prognostic groups. The primary endpoint,previously reported, was progression-free survival, and HRQOL was a secondary endpoint.Most HRQOL analyses were done in patients who underwent randomisation, received atleast one dose of study treatment, and had any HRQOL data. Completion and complianceanalyses were done in the full analysis set. Functional Assessment of Cancer TherapyKidney Symptom Index-Disease-Related Symptoms (FKSI-DRS), European Organisation forthe Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTCQLQ-C30), and the EQ-5D-3 Level (EQ-5D-3L) preference questionnaire were administeredat baseline and on day 1 of each subsequent 21-day cycle. This study is registeredwith ClinicalTrials.gov, NCT02811861, and is closed to new participants. Findings : Between Oct 13, 2016, and July 24, 2019, 355 patients were randomly assigned to the lenvatinib plus pembrolizumab group, 357 to the lenvatinib plus everolimus group,and 357 to the sunitinib group. Median follow-up for HRQOL analyses was 12·9 months(IQR 5·6–22·3). Because of the promising efficacy and safety results of lenvatinibplus pembrolizumab in the first-line setting, we focus the HRQOL results in this reporton that combination versus sunitinib. Mean change from baseline in the lenvatinibplus pembrolizumab group compared with the sunitinib group was –1·75 (SE 0·59) versus –2·19 (0·66) for FKSI-DRS, –5·93 (0·86) versus –6·73 (0·94) for EORTC QLQ-C30 globalhealth status/quality of life (GHS/QOL), and –4·96 (0·85) versus –6·64 (0·94) forthe EQ-5D visual analogue scale (VAS). Median time to first deterioration in the lenvatinibplus pembrolizumab group compared with the sunitinib group was 9·14 weeks (95% CI6·43–12·14) versus 12·14 weeks (9·14–15·29; HR 1·13 [95% CI 0·94–1·35], log-rank p=0·20)for FKSI-DRS, 12·00 weeks (7·29–15·14) versus 9·14 weeks (6·29–12·14; 0·88 [0·74–1·05],log-rank p=0·17) for EORTC QLQ-C30 GHS/QOL, and 9·43 weeks (6·43–12·29) versus 9·14weeks (6·29–12·00; 0·83 [0·70–0·99], log-rank p=0·041) for the EQ-5D VAS. Median timeto definitive deterioration in the lenvatinib plus pembrolizumab group compared withthe sunitinib group was 134·14 weeks (95% CI 120·00–not estimable) versus 117·43 weeks(90·14–131·29; HR 0·70 [95% CI 0·53–0·92], log-rank p=0·0081) for FKSI-DRS, 114·29weeks (102·14–153·29) versus 75·14 weeks (57·29–105·14; 0·60 [0·47–0·77], log-rankp<0·0001) for EORTC QLQ-C30 GHS/QOL, and 124·86 weeks (94·71–134·57) versus 74·86weeks (54·14–96·00; 0·67 [0·53–0·85], log-rank p=0·0012) for the EQ-5D VAS. No outcomeson any of the instruments significantly favoured sunitinib over lenvatinib plus pembrolizumab.Most HRQOL comparisons of lenvatinib plus everolimus versus sunitinib were similaror favoured sunitinib. Interpretation : These HRQOL results demonstrate that patients given lenvatinib plus pembrolizumabtreatment had similar or favourable 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.
The Lancet Oncology 2022