Phase 3 CLEAR study in patients with advanced renal cell carcinoma: outcomes in subgroups for the lenvatinib-plus-pembrolizumab and sunitinib arms

V. Grünwald; Grünwald V.; T. Powles; Powles T.; M. Eto; Eto M.; E. Kopyltsov; Kopyltsov E.; S. Y. Rha; Rha S. Y.; C. Porta; Porta C.; R. Motzer; Motzer R.; T. E. Hutson; Hutson T. E.; M. J. Méndez-Vidal; Méndez-Vidal M. J.; S. H. Hong; Hong S. H.; E. Winquist; Winquist E.; J. C. Goh; Goh J. C.; P. Maroto; Maroto P.; T. Buchler; Buchler T.; T. Takagi; Takagi T.; J. E. Burgents; Burgents J. E.; R. Perini; Perini R.; C. He; He C.; C. E. Okpara; Okpara C. E.; J. McKenzie; McKenzie J.; T. K. Choueiri; Choueiri T. K.

doi:10.17650/1726-9776-2024-20-1-24-35

Phase 3 CLEAR study in patients with advanced renal cell carcinoma: outcomes in subgroups for the lenvatinib-plus-pembrolizumab and sunitinib arms

Authors: Grünwald V.¹, Powles T.², Eto M.³, Kopyltsov E.⁴, Rha S.Y.⁵, Porta C.⁶, Motzer R.⁷, Hutson T.E.⁸, Méndez-Vidal M.J.⁹, Hong S.H.¹⁰, Winquist E.¹¹, Goh J.C.¹², Maroto P.¹³, Buchler T.¹⁴, Takagi T.¹⁵, Burgents J.E.¹⁶, Perini R.¹⁷, He C.¹⁸, Okpara C.E.¹⁹, McKenzie J.²⁰, Choueiri T.K.²¹
Affiliations:
1. Clinic for Medical Oncology and Clinic for Urology, University Hospital Essen
2. Barts Cancer Institute and the Royal Free Hospital, Queen Mary University of London
3. Department of Urology, Kyushu University
4. State Institution of Healthcare Regional Clinical Oncology Dispensary
5. Department of Internal Medicine, Yonsei Cancer Center, Yonsei University Health System
6. Department of Biomedical Sciences and Human Oncology, University of Bari ‘A. Moro’
7. Department of Medicine, Memorial Sloan Kettering Cancer Center
8. Medical Oncology, Texas Oncology
9. Department of Oncology, Maimonides Institute for Biomedical Research of Córdoba (IMIBIC) Hospital Universitario Reina Sofía
10. Department of Urology, Seoul St. Mary’s Hospital, The Catholic University of Korea
11. Department of Oncology, University of Western Ontario
12. ICON Research, South Brisbane & University of Queensland ICON Research
13. Department of Medical Oncology, Hospital de la Santa Creu i Sant Pau
14. Department of Oncology, Charles University and Thomayer University Hospital
15. Department of Urology, Tokyo Women’s Medical University
16. Global Clinical Development, Merck & Co., Inc.
17. Clinical Research, Merck & Co., Inc.
18. Biostatistics, Eisai Inc.
19. Clinical Research, Eisai Ltd.
20. Clinical Research, Eisai Inc.
21. Department of Medical Oncology, Dana-Farber Cancer Institute
Issue: Vol 20, No 1 (2024)
Pages: 24-35
Section: DIAGNOSIS AND TREATMENT OF URINARY SYSTEM TUMORS. RENAL CANCER
Published: 18.05.2024
URL: https://oncourology.abvpress.ru/oncur/article/view/1810
DOI: https://doi.org/10.17650/1726-9776-2024-20-1-24-35
ID: 1810

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Abstract

Introduction. The phase 3 CLEAR study demonstrated that lenvatinib plus pembrolizumab significantly improved efficacy versus sunitinib as first-line treatment for patients with advanced renal cell carcinoma (RCC). Prognostic features including presence and/or site of baseline metastases, prior nephrectomy, and sarcomatoid features have been associated with disease and treatment success. This subsequent analysis explores outcomes in patients with or without specific prognostic features.

Methods. In CLEAR, patients with clear cell RCC were randomly assigned (1:1:1) to receive either lenvatinib (20 mg/day) plus pembrolizumab (200 mg every 3 weeks), lenvatinib (18 mg/day) plus everolimus (5 mg/day), or sunitinib alone (50 mg/day, 4 weeks on, 2 weeks off). In this report, progression-free survival, overall survival, and objective response rate were all assessed in the lenvatinib-plus-pembrolizumab and the sunitinib arms, based on baseline features: lung metastases, bone metastases, liver metastases, prior nephrectomy, and sarcomatoid histology.

Results. In all the assessed subgroups, median progression-free survival was longer with lenvatinib plus-pembrolizumab than with sunitinib treatment, notably among patients with baseline bone metastases (hazard ratio (HR) 0.33; 95 % confidence interval (CI) 0.21–0.52) and patients with sarcomatoid features (HR 0.39; 95 % CI 0.18–0.84). Median overall survival favored lenvatinib plus pembrolizumab over sunitinib irrespective of metastatic lesions at baseline, prior nephrectomy, and sarcomatoid features. Of interest, among patients with baseline bone metastases the HR for survival was 0.50 (95 % CI 0.30–0.83) and among patients with sarcomatoid features the HR for survival was 0.91 (95 % CI 0.32–2.58); though for many groups, median overall survival was not reached. Objective response rate also favored lenvatinib plus pembrolizumab over sunitinib across all subgroups; similarly, complete responses also followed this pattern.

Conclusion. Efficacy outcomes improved following treatment with lenvatinib-plus-pembrolizumab versus sunitinib in patients with RCC – irrespective of the presence or absence of baseline lung metastases, baseline bone metastases, baseline liver metastases, prior nephrectomy, or sarcomatoid features. These findings corroborate those of the primary CLEAR study analysis in the overall population and support lenvatinib plus pembrolizumab as a standard of care in 1L treatment for patients with advanced RCC.