Detail
Article
Online article
FT
Medvik - BMC
  • Something wrong with this record ?

Lenvatinib Plus Pembrolizumab Versus Sunitinib in First-Line Treatment of Advanced Renal Cell Carcinoma: Final Prespecified Overall Survival Analysis of CLEAR, a Phase III Study

RJ. Motzer, C. Porta, M. Eto, T. Powles, V. Grünwald, TE. Hutson, B. Alekseev, SY. Rha, J. Merchan, JC. Goh, AA. Lalani, U. De Giorgi, B. Melichar, SH. Hong, H. Gurney, MJ. Méndez-Vidal, E. Kopyltsov, S. Tjulandin, TA. Gordoa, V. Kozlov, A....

. 2024 ; 42 (11) : 1222-1228. [pub] 20240116

Language English Country United States

Document type Randomized Controlled Trial, Clinical Trial, Phase III, Journal Article

Grant support
P30 CA008748 NCI NIH HHS - United States

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical trial updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.We present the final prespecified overall survival (OS) analysis of the open-label, phase III CLEAR study in treatment-naïve patients with advanced renal cell carcinoma (aRCC). With an additional follow-up of 23 months from the primary analysis, we report results from the lenvatinib plus pembrolizumab versus sunitinib comparison of CLEAR. Treatment-naïve patients with aRCC were randomly assigned to receive lenvatinib (20 mg orally once daily in 21-day cycles) plus pembrolizumab (200 mg intravenously once every 3 weeks) or sunitinib (50 mg orally once daily [4 weeks on/2 weeks off]). At this data cutoff date (July 31, 2022), the OS hazard ratio (HR) was 0.79 (95% CI, 0.63 to 0.99). The median OS (95% CI) was 53.7 months (95% CI, 48.7 to not estimable [NE]) with lenvatinib plus pembrolizumab versus 54.3 months (95% CI, 40.9 to NE) with sunitinib; 36-month OS rates (95% CI) were 66.4% (95% CI, 61.1 to 71.2) and 60.2% (95% CI, 54.6 to 65.2), respectively. The median progression-free survival (95% CI) was 23.9 months (95% CI, 20.8 to 27.7) with lenvatinib plus pembrolizumab and 9.2 months (95% CI, 6.0 to 11.0) with sunitinib (HR, 0.47 [95% CI, 0.38 to 0.57]). Objective response rate also favored the combination over sunitinib (71.3% v 36.7%; relative risk 1.94 [95% CI, 1.67 to 2.26]). Treatment-emergent adverse events occurred in >90% of patients who received either treatment. In conclusion, lenvatinib plus pembrolizumab achieved consistent, durable benefit with a manageable safety profile in treatment-naïve patients with aRCC.

Dana Farber Cancer Institute Boston MA

Department of Urology and Transplantation Surgery Klinikum Stuttgart Stuttgart Germany

Department of Urology Medical University of Vienna Vienna Austria

Eisai Inc Nutley NJ

Eisai Ltd Hatfield UK

Fondazione IRCCS Istituto Nazionale Tumori Milano Milan Italy

Hospital de la Santa Creu i Sant Pau Barcelona Spain

Hospital Universitario Ramón y Cajal Madrid Spain

ICON Research South Brisbane and Queensland University of Technology Brisbane Queensland Australia

IRCCS Istituto Romagnolo per lo Studio dei Tumori Dino Amadori Meldola Italy

Juravinski Cancer Centre McMaster University Hamilton Ontario Canada

Kyushu University Fukuoka Japan

Macquarie University Sydney NSW Australia

Maimonides Institute for Biomedical research of Cordoba Hospital Universitario Reina Sofía Medical Oncology Department Córdoba Spain

Memorial Sloan Kettering Cancer Center New York NY

Merck and Co Inc Kenilworth NJ

Merck and Co Inc Rahway NJ

N N Blokhin National Medical Research Center for Oncology Ministry of Health of the Russian Federation Moscow Russia

P A Herzen Moscow Oncological Research Institute Moscow Russia

Palacky University and University Hospital Olomouc Olomouc Czech Republic

Prevoljskiy Region Medical Centre Novgorod Russia

Rambam Health Care Campus Haifa Israel

Seoul National University Hospital Seoul South Korea

Seoul St Mary's Hospital The Catholic University of Korea Seoul South Korea

State budgetary Health Care Institution Novosibirsk Regional Clinical Oncology Dispensary Novosibirsk Russia

State Institution of Healthcare Regional Clinical Oncology Dispensary Omsk Russia

Texas Oncology Dallas TX

The Royal Free NHS Trust London United Kingdom

Tokyo Women's Medical University Tokyo Japan

University Hospital Essen Essen Germany

University of Bari A Moro Bari Italy

University of Miami Sylvester Comprehensive Cancer Center Miami FL

University of Pavia Pavia Italy

Western Health Melbourne Victoria Australia

Western University London Ontario Canada

Yonsei Cancer Center Yonsei University Health System Seoul South Korea

References provided by Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc24014342
003      
CZ-PrNML
005      
20240905133442.0
007      
ta
008      
240725s2024 xxu f 000 0|eng||
009      
AR
024    7_
$a 10.1200/JCO.23.01569 $2 doi
035    __
$a (PubMed)38227898
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a xxu
100    1_
$a Motzer, Robert J $u Memorial Sloan Kettering Cancer Center, New York, NY $1 https://orcid.org/0000000169252327
245    10
$a Lenvatinib Plus Pembrolizumab Versus Sunitinib in First-Line Treatment of Advanced Renal Cell Carcinoma: Final Prespecified Overall Survival Analysis of CLEAR, a Phase III Study / $c RJ. Motzer, C. Porta, M. Eto, T. Powles, V. Grünwald, TE. Hutson, B. Alekseev, SY. Rha, J. Merchan, JC. Goh, AA. Lalani, U. De Giorgi, B. Melichar, SH. Hong, H. Gurney, MJ. Méndez-Vidal, E. Kopyltsov, S. Tjulandin, TA. Gordoa, V. Kozlov, A. Alyasova, E. Winquist, P. Maroto, M. Kim, A. Peer, G. Procopio, T. Takagi, S. Wong, J. Bedke, M. Schmidinger, K. Rodriguez-Lopez, J. Burgents, C. He, CE. Okpara, J. McKenzie, TK. Choueiri, CLEAR Trial Investigators
520    9_
$a Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical trial updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.We present the final prespecified overall survival (OS) analysis of the open-label, phase III CLEAR study in treatment-naïve patients with advanced renal cell carcinoma (aRCC). With an additional follow-up of 23 months from the primary analysis, we report results from the lenvatinib plus pembrolizumab versus sunitinib comparison of CLEAR. Treatment-naïve patients with aRCC were randomly assigned to receive lenvatinib (20 mg orally once daily in 21-day cycles) plus pembrolizumab (200 mg intravenously once every 3 weeks) or sunitinib (50 mg orally once daily [4 weeks on/2 weeks off]). At this data cutoff date (July 31, 2022), the OS hazard ratio (HR) was 0.79 (95% CI, 0.63 to 0.99). The median OS (95% CI) was 53.7 months (95% CI, 48.7 to not estimable [NE]) with lenvatinib plus pembrolizumab versus 54.3 months (95% CI, 40.9 to NE) with sunitinib; 36-month OS rates (95% CI) were 66.4% (95% CI, 61.1 to 71.2) and 60.2% (95% CI, 54.6 to 65.2), respectively. The median progression-free survival (95% CI) was 23.9 months (95% CI, 20.8 to 27.7) with lenvatinib plus pembrolizumab and 9.2 months (95% CI, 6.0 to 11.0) with sunitinib (HR, 0.47 [95% CI, 0.38 to 0.57]). Objective response rate also favored the combination over sunitinib (71.3% v 36.7%; relative risk 1.94 [95% CI, 1.67 to 2.26]). Treatment-emergent adverse events occurred in >90% of patients who received either treatment. In conclusion, lenvatinib plus pembrolizumab achieved consistent, durable benefit with a manageable safety profile in treatment-naïve patients with aRCC.
650    _2
$a lidé $7 D006801
650    12
$a karcinom z renálních buněk $x patologie $7 D002292
650    _2
$a sunitinib $x škodlivé účinky $7 D000077210
650    12
$a nádory ledvin $x patologie $7 D007680
650    _2
$a protokoly protinádorové kombinované chemoterapie $x škodlivé účinky $7 D000971
650    _2
$a analýza přežití $7 D016019
650    12
$a fenylmočovinové sloučeniny $7 D010671
650    12
$a chinoliny $7 D011804
650    12
$a humanizované monoklonální protilátky $7 D061067
655    _2
$a randomizované kontrolované studie $7 D016449
655    _2
$a klinické zkoušky, fáze III $7 D017428
655    _2
$a časopisecké články $7 D016428
700    1_
$a Porta, Camillo $u University of Bari "A. Moro," Bari, Italy $u University of Pavia, Pavia, Italy
700    1_
$a Eto, Masatoshi $u Kyushu University, Fukuoka, Japan
700    1_
$a Powles, Thomas $u The Royal Free NHS Trust, London, United Kingdom $1 https://orcid.org/0000000177604724
700    1_
$a Grünwald, Viktor $u University Hospital Essen, Essen, Germany $1 https://orcid.org/0000000320837687
700    1_
$a Hutson, Thomas E $u Texas Oncology, Dallas, TX $1 https://orcid.org/0000000245294212
700    1_
$a Alekseev, Boris $u P.A. Herzen Moscow Oncological Research Institute, Moscow, Russia
700    1_
$a Rha, Sun Young $u Yonsei Cancer Center, Yonsei University Health System, Seoul, South Korea $1 https://orcid.org/0000000225124531
700    1_
$a Merchan, Jaime $u University of Miami Sylvester Comprehensive Cancer Center, Miami, FL $1 https://orcid.org/0000000337524134
700    1_
$a Goh, Jeffrey C $u ICON Research, South Brisbane & Queensland University of Technology, Brisbane, Queensland, Australia $1 https://orcid.org/000000033103146X
700    1_
$a Lalani, Aly-Khan A $u Juravinski Cancer Centre, McMaster University, Hamilton, Ontario, Canada $1 https://orcid.org/0000000299079112
700    1_
$a De Giorgi, Ugo $u IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) Dino Amadori, Meldola, Italy $1 https://orcid.org/0000000175202908
700    1_
$a Melichar, Bohuslav $u Palacky University, and University Hospital Olomouc, Olomouc, Czech Republic
700    1_
$a Hong, Sung-Hoo $u Seoul St Mary's Hospital, The Catholic University of Korea, Seoul, South Korea $1 https://orcid.org/0000000219524010
700    1_
$a Gurney, Howard $u Macquarie University, Sydney, NSW, Australia $1 https://orcid.org/0000000302175261
700    1_
$a Méndez-Vidal, María José $u Maimonides Institute for Biomedical research of Cordoba (IMIBIC) Hospital Universitario Reina Sofía, Medical Oncology Department, Córdoba, Spain $1 https://orcid.org/0000000274601859
700    1_
$a Kopyltsov, Evgeny $u State Institution of Healthcare "Regional Clinical Oncology Dispensary," Omsk, Russia
700    1_
$a Tjulandin, Sergei $u N N Blokhin National Medical Research Center for Oncology, Ministry of Health of the Russian Federation, Moscow, Russia $1 https://orcid.org/0000000198072229
700    1_
$a Gordoa, Teresa Alonso $u Hospital Universitario Ramón y Cajal, Madrid, Spain $1 https://orcid.org/0000000289667236
700    1_
$a Kozlov, Vadim $u State budgetary Health Care Institution "Novosibirsk Regional Clinical Oncology Dispensary," Novosibirsk, Russia
700    1_
$a Alyasova, Anna $u Prevoljskiy Region Medical Centre, Novgorod, Russia
700    1_
$a Winquist, Eric $u Western University, London, Ontario, Canada $1 https://orcid.org/0000000288295979
700    1_
$a Maroto, Pablo $u Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
700    1_
$a Kim, Miso $u Seoul National University Hospital, Seoul, South Korea $1 https://orcid.org/0000000240644199
700    1_
$a Peer, Avivit $u Rambam Health Care Campus, Haifa, Israel
700    1_
$a Procopio, Giuseppe $u Fondazione IRCCS Istituto Nazionale Tumori Milano, Milan, Italy $1 https://orcid.org/000000022498402X
700    1_
$a Takagi, Toshio $u Tokyo Women's Medical University, Tokyo, Japan
700    1_
$a Wong, Shirley $u Western Health, Melbourne, Victoria, Australia
700    1_
$a Bedke, Jens $u Department of Urology and Transplantation Surgery, Klinikum Stuttgart, Stuttgart, Germany $1 https://orcid.org/0000000327783108
700    1_
$a Schmidinger, Manuela $u Department of Urology, Medical University of Vienna, Vienna, Austria
700    1_
$a Rodriguez-Lopez, Karla $u Merck & Co, Inc, Rahway, NJ
700    1_
$a Burgents, Joseph $u Merck & Co, Inc, Kenilworth, NJ
700    1_
$a He, Cixin $u Eisai Inc, Nutley, NJ
700    1_
$a Okpara, Chinyere E $u Eisai Ltd, Hatfield, UK $1 https://orcid.org/0000000256219138
700    1_
$a McKenzie, Jodi $u Eisai Inc, Nutley, NJ $1 https://orcid.org/0000000263451218
700    1_
$a Choueiri, Toni K $u Dana-Farber Cancer Institute, Boston, MA $1 https://orcid.org/0000000292013217
710    2_
$a CLEAR Trial Investigators
773    0_
$w MED00002596 $t Journal of clinical oncology $x 1527-7755 $g Roč. 42, č. 11 (2024), s. 1222-1228
856    41
$u https://pubmed.ncbi.nlm.nih.gov/38227898 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y - $z 0
990    __
$a 20240725 $b ABA008
991    __
$a 20240905133436 $b ABA008
999    __
$a ok $b bmc $g 2143863 $s 1226208
BAS    __
$a 3
BAS    __
$a PreBMC-MEDLINE
BMC    __
$a 2024 $b 42 $c 11 $d 1222-1228 $e 20240116 $i 1527-7755 $m Journal of clinical oncology $n J Clin Oncol $x MED00002596
GRA    __
$a P30 CA008748 $p NCI NIH HHS $2 United States
LZP    __
$a Pubmed-20240725

Find record

Citation metrics

Loading data ...

Archiving options

Loading data ...