Belzutifan versus Everolimus for Advanced Renal-Cell Carcinoma

J 2024

Belzutifan versus Everolimus for Advanced Renal-Cell Carcinoma

CHOUEIRI, T. K., T. POWLES, K. PELTOLA, G. DE VELASCO, M. BUROTTO et. al.

Basic information

Original name

Belzutifan versus Everolimus for Advanced Renal-Cell Carcinoma

Authors

CHOUEIRI, T. K., T. POWLES, K. PELTOLA, G. DE VELASCO, M. BUROTTO, C. SUAREZ, P. GHATALIA, R. IACOVELLI, E. T. LAM, E. VERZONI, M. GUMUS, W. M. STADLER, C. KOLLMANNSBERGER, B. MELICHAR, B. VENUGOPAL, M. GROSS-GOUPIL, Alexandr POPRACH (203 Czech Republic, belonging to the institution), M. DE SANTIS, F. A. SCHUTZ, S. H. PARK, D. A. NOSOV, C. PORTA, J. L. LEE, X. GARCIA-DEL-MURO, E. BISCALDI, R Manneh KOPP, M. OYA, L. HE, A. WANG, R. F. PERINI, D. VICKERY, L. ALBIGES and B. RINI

Edition

New England Journal of Medicine, Waltham, Massachussetts Medical Society, 2024, 0028-4793

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30204 Oncology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 158.500 in 2022

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1056/NEJMoa2313906

UT WoS

001301684200012

Keywords in English

Belzutifan; Everolimus; Advanced Renal-Cell Carcinoma

Abstract

V originále

Background Belzutifan, a hypoxia-inducible factor 2 alpha inhibitor, showed clinical activity in clear-cell renal-cell carcinoma in early-phase studies. Methods In a phase 3, multicenter, open-label, active-controlled trial, we enrolled participants with advanced clear-cell renal-cell carcinoma who had previously received immune checkpoint and antiangiogenic therapies and randomly assigned them, in a 1:1 ratio, to receive 120 mg of belzutifan or 10 mg of everolimus orally once daily until disease progression or unacceptable toxic effects occurred. The dual primary end points were progression-free survival and overall survival. The key secondary end point was the occurrence of an objective response (a confirmed complete or partial response). Download a PDF of the Plain Language Summary. Results A total of 374 participants were assigned to belzutifan, and 372 to everolimus. At the first interim analysis (median follow-up, 18.4 months), the median progression-free survival was 5.6 months in both groups; at 18 months, 24.0% of the participants in the belzutifan group and 8.3% in the everolimus group were alive and free of progression (two-sided P=0.002, which met the prespecified significance criterion). A confirmed objective response occurred in 21.9% of the participants (95% confidence interval [CI], 17.8 to 26.5) in the belzutifan group and in 3.5% (95% CI, 1.9 to 5.9) in the everolimus group (P<0.001, which met the prespecified significance criterion). At the second interim analysis (median follow-up, 25.7 months), the median overall survival was 21.4 months in the belzutifan group and 18.1 months in the everolimus group; at 18 months, 55.2% and 50.6% of the participants, respectively, were alive (hazard ratio for death, 0.88; 95% CI, 0.73 to 1.07; two-sided P=0.20, which did not meet the prespecified significance criterion). Grade 3 or higher adverse events of any cause occurred in 61.8% of the participants in the belzutifan group (grade 5 in 3.5%) and in 62.5% in the everolimus group (grade 5 in 5.3%). Adverse events led to discontinuation of treatment in 5.9% and 14.7% of the participants, respectively. Conclusions Belzutifan showed a significant benefit over everolimus with respect to progression-free survival and objective response in participants with advanced clear-cell renal-cell carcinoma who had previously received immune checkpoint and antiangiogenic therapies. Belzutifan was associated with no new safety signals. (Funded by Merck Sharp and Dohme, a subsidiary of Merck; LITESPARK-005 ClinicalTrials.gov number, NCT04195750.)

Citovat

CHOUEIRI, T. K., T. POWLES, K. PELTOLA, G. DE VELASCO, M. BUROTTO, C. SUAREZ, P. GHATALIA, R. IACOVELLI, E. T. LAM, E. VERZONI, M. GUMUS, W. M. STADLER, C. KOLLMANNSBERGER, B. MELICHAR, B. VENUGOPAL, M. GROSS-GOUPIL, Alexandr POPRACH, M. DE SANTIS, F. A. SCHUTZ, S. H. PARK, D. A. NOSOV, C. PORTA, J. L. LEE, X. GARCIA-DEL-MURO, E. BISCALDI, R Manneh KOPP, M. OYA, L. HE, A. WANG, R. F. PERINI, D. VICKERY, L. ALBIGES and B. RINI. Belzutifan versus Everolimus for Advanced Renal-Cell Carcinoma. New England Journal of Medicine. Waltham: Massachussetts Medical Society, 2024, vol. 391, No 8, p. 710-721. ISSN 0028-4793. Available from: https://dx.doi.org/10.1056/NEJMoa2313906.

@article{2436160,
   author = {Choueiri, T. K. and Powles, T. and Peltola, K. and de Velasco, G. and Burotto, M. and Suarez, C. and Ghatalia, P. and Iacovelli, R. and Lam, E. T. and Verzoni, E. and Gumus, M. and Stadler, W. M. and Kollmannsberger, C. and Melichar, B. and Venugopal, B. and GrossandGoupil, M. and Poprach, Alexandr and De Santis, M. and Schutz, F. A. and Park, S. H. and Nosov, D. A. and Porta, C. and Lee, J. L. and GarciaanddelandMuro, X. and Biscaldi, E. and Kopp, R Manneh and Oya, M. and He, L. and Wang, A. and Perini, R. F. and Vickery, D. and Albiges, L. and Rini, B.},
   article_location = {Waltham},
   article_number = {8},
   doi = {http://dx.doi.org/10.1056/NEJMoa2313906},
   keywords = {Belzutifan; Everolimus; Advanced Renal-Cell Carcinoma},
   language = {eng},
   issn = {0028-4793},
   journal = {New England Journal of Medicine},
   title = {Belzutifan versus Everolimus for Advanced Renal-Cell Carcinoma},
   url = {https://www.nejm.org/doi/10.1056/NEJMoa2313906},
   volume = {391},
   year = {2024}
}

TY  - JOUR
ID  - 2436160
AU  - Choueiri, T. K. - Powles, T. - Peltola, K. - de Velasco, G. - Burotto, M. - Suarez, C. - Ghatalia, P. - Iacovelli, R. - Lam, E. T. - Verzoni, E. - Gumus, M. - Stadler, W. M. - Kollmannsberger, C. - Melichar, B. - Venugopal, B. - Gross-Goupil, M. - Poprach, Alexandr - De Santis, M. - Schutz, F. A. - Park, S. H. - Nosov, D. A. - Porta, C. - Lee, J. L. - Garcia-del-Muro, X. - Biscaldi, E. - Kopp, R Manneh - Oya, M. - He, L. - Wang, A. - Perini, R. F. - Vickery, D. - Albiges, L. - Rini, B.
PY  - 2024
TI  - Belzutifan versus Everolimus for Advanced Renal-Cell Carcinoma
JF  - New England Journal of Medicine
VL  - 391
IS  - 8
SP  - 710-721
EP  - 710-721
PB  - Massachussetts Medical Society
SN  - 00284793
KW  - Belzutifan
KW  - Everolimus
KW  - Advanced Renal-Cell Carcinoma
UR  - https://www.nejm.org/doi/10.1056/NEJMoa2313906
N2  - Background Belzutifan, a hypoxia-inducible factor 2 alpha inhibitor, showed clinical activity in clear-cell renal-cell carcinoma in early-phase studies. Methods In a phase 3, multicenter, open-label, active-controlled trial, we enrolled participants with advanced clear-cell renal-cell carcinoma who had previously received immune checkpoint and antiangiogenic therapies and randomly assigned them, in a 1:1 ratio, to receive 120 mg of belzutifan or 10 mg of everolimus orally once daily until disease progression or unacceptable toxic effects occurred. The dual primary end points were progression-free survival and overall survival. The key secondary end point was the occurrence of an objective response (a confirmed complete or partial response). Download a PDF of the Plain Language Summary. Results A total of 374 participants were assigned to belzutifan, and 372 to everolimus. At the first interim analysis (median follow-up, 18.4 months), the median progression-free survival was 5.6 months in both groups; at 18 months, 24.0% of the participants in the belzutifan group and 8.3% in the everolimus group were alive and free of progression (two-sided P=0.002, which met the prespecified significance criterion). A confirmed objective response occurred in 21.9% of the participants (95% confidence interval [CI], 17.8 to 26.5) in the belzutifan group and in 3.5% (95% CI, 1.9 to 5.9) in the everolimus group (P<0.001, which met the prespecified significance criterion). At the second interim analysis (median follow-up, 25.7 months), the median overall survival was 21.4 months in the belzutifan group and 18.1 months in the everolimus group; at 18 months, 55.2% and 50.6% of the participants, respectively, were alive (hazard ratio for death, 0.88; 95% CI, 0.73 to 1.07; two-sided P=0.20, which did not meet the prespecified significance criterion). Grade 3 or higher adverse events of any cause occurred in 61.8% of the participants in the belzutifan group (grade 5 in 3.5%) and in 62.5% in the everolimus group (grade 5 in 5.3%). Adverse events led to discontinuation of treatment in 5.9% and 14.7% of the participants, respectively. Conclusions Belzutifan showed a significant benefit over everolimus with respect to progression-free survival and objective response in participants with advanced clear-cell renal-cell carcinoma who had previously received immune checkpoint and antiangiogenic therapies. Belzutifan was associated with no new safety signals. (Funded by Merck Sharp and Dohme, a subsidiary of Merck; LITESPARK-005 ClinicalTrials.gov number, NCT04195750.)
ER  -

CHOUEIRI, T. K., T. POWLES, K. PELTOLA, G. DE VELASCO, M. BUROTTO, C. SUAREZ, P. GHATALIA, R. IACOVELLI, E. T. LAM, E. VERZONI, M. GUMUS, W. M. STADLER, C. KOLLMANNSBERGER, B. MELICHAR, B. VENUGOPAL, M. GROSS-GOUPIL, Alexandr POPRACH, M. DE SANTIS, F. A. SCHUTZ, S. H. PARK, D. A. NOSOV, C. PORTA, J. L. LEE, X. GARCIA-DEL-MURO, E. BISCALDI, R Manneh KOPP, M. OYA, L. HE, A. WANG, R. F. PERINI, D. VICKERY, L. ALBIGES and B. RINI. Belzutifan versus Everolimus for Advanced Renal-Cell Carcinoma. \textit{New England Journal of Medicine}. Waltham: Massachussetts Medical Society, 2024, vol.~391, No~8, p.~710-721. ISSN~0028-4793. Available from: https://dx.doi.org/10.1056/NEJMoa2313906.

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