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Long-term outcomes among patients who respond within the first year to nivolumab plus ipilimumab or nivolumab monotherapy: A pooled analysis in 935 patients

C. Robert, G.V. Long, J. Larkin, J.D. Wolchok, J.C. Hassel, D. Schadendorf, F.S. Hodi, C. Lebbé, J.-J. Grob, J.R. Hyngstrom, John Wagstaff, J. Chesney, M.O. Butler, O. Bechter, I. Márquez-Rodas, A.C. Pavlick, P. Durani, M. Pe Benito, P. Wang, M.A. Postow, P.A. Ascierto

European Journal of Cancer, Volume: 214, Start page: 115119

Swansea University Author: John Wagstaff

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DOI (Published version): 10.1016/j.ejca.2024.115119

Abstract

Purpose: To investigate the predictive value of RECIST response within 3, 6, or 12 months on long-term survival, and explore differences between nivolumab+ipilimumab and nivolumab monotherapy, we analyzed pooled 5-year data of 935 responder and non-responder patients at various time points after tre...

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Published in: European Journal of Cancer
ISSN: 0959-8049 1879-0852
Published: Elsevier BV 2025
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URI: https://cronfa.swan.ac.uk/Record/cronfa68590
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Patients and methods: Treatment-naive advanced melanoma patients received nivolumab+ipilimumab or nivolumab monotherapy. To decrease immortal time bias, 3-, 6-, or 12-month overall survival (OS) and progression-free survival (PFS) landmark analyses were performed. Association between characteristics and response was evaluated by univariate and multivariate analyses. Results: Response rates at any time were 58&#xA0;% (239/409) for nivolumab+ipilimumab and 44&#xA0;% (230/526) for nivolumab monotherapy. In 12-month landmark analyses, 5-year OS rates for responders versus non-responders were 82&#xA0;% versus 40&#xA0;% with nivolumab+ipilimumab (HR=0.23 [95&#xA0;% CI, 0.15-0.35]) and 76&#xA0;% versus 32&#xA0;% with nivolumab monotherapy (HR=0.22 [95&#xA0;% CI, 0.16-0.31]). PFS rates were 83&#xA0;% versus 32&#xA0;% and 69&#xA0;% versus 46&#xA0;%, respectively. Similar strong associations between response at 3 and 6 months and 5-year OS and PFS were also observed with more than 70&#xA0;% of the responses observed in the first 3 months. Response rates correlated with baseline LDH and PD-L1 status by multivariate analysis but the association between response and long-term survival was maintained in landmark analyses even among patients with high LDH and low PD-L1 expression. Conclusion: Clinical response evaluated in the first months of therapy is a strong predictor of long-term survival, even in patients with poor prognostic biomarkers.</abstract><type>Journal Article</type><journal>European Journal of Cancer</journal><volume>214</volume><journalNumber/><paginationStart>115119</paginationStart><paginationEnd/><publisher>Elsevier BV</publisher><placeOfPublication/><isbnPrint/><isbnElectronic/><issnPrint>0959-8049</issnPrint><issnElectronic>1879-0852</issnElectronic><keywords>Clinical response; Long-term survival; Advanced melanoma; Nivolumab; Ipilimumab; Prognostic factors</keywords><publishedDay>1</publishedDay><publishedMonth>1</publishedMonth><publishedYear>2025</publishedYear><publishedDate>2025-01-01</publishedDate><doi>10.1016/j.ejca.2024.115119</doi><url/><notes/><college>COLLEGE NANME</college><department>Medical School</department><CollegeCode>COLLEGE CODE</CollegeCode><DepartmentCode>MEDS</DepartmentCode><institution>Swansea University</institution><apcterm>Another institution paid the OA fee</apcterm><funders>The authors thank the patients and investigators who participated in the CheckMate 069, 066 and 067 trials. They acknowledge Ono Pharmaceutical Company, Ltd. (Osaka, Japan) for contributions to nivolumab development and Dako, an Agilent Technologies, Inc. company (Santa Clara, CA) for collaborative development of the PD-L1 immunohistochemistry 28&#x2013;8 pharmDx assay. The authors thank Wim van Dijck from Bristol Myers Squibb for statistical contributions for the study, as well as Sandra Re and Jasmine Rizzo from Bristol Myers Squibb for medical oversight. Professional medical writing and editorial assistance were provided by Melissa Kirk, PhD, and Michele Salernitano at Ashfield MedComms, an Inizio Company, funded by Bristol Myers Squibb. M. Postow acknowledges support from the NIH/NCI Cancer Center Support Grant P30 CA008748. J. Wagstaff acknowledges grant support MSK P30 CA008748. J. Larkin acknowledges grant support from the National Institute for Health Research Royal Marsden-Institute of Cancer Research Biomedical Research Centre. This work was supported by Bristol Myers Squibb (Princeton, NJ).</funders><projectreference/><lastEdited>2025-01-29T13:58:56.6044799</lastEdited><Created>2024-12-18T12:19:36.4629088</Created><path><level id="1">Faculty of Medicine, Health and Life Sciences</level><level id="2">Swansea University Medical School - Biomedical Science</level></path><authors><author><firstname>C.</firstname><surname>Robert</surname><order>1</order></author><author><firstname>G.V.</firstname><surname>Long</surname><order>2</order></author><author><firstname>J.</firstname><surname>Larkin</surname><order>3</order></author><author><firstname>J.D.</firstname><surname>Wolchok</surname><order>4</order></author><author><firstname>J.C.</firstname><surname>Hassel</surname><order>5</order></author><author><firstname>D.</firstname><surname>Schadendorf</surname><order>6</order></author><author><firstname>F.S.</firstname><surname>Hodi</surname><order>7</order></author><author><firstname>C.</firstname><surname>Lebb&#xE9;</surname><order>8</order></author><author><firstname>J.-J.</firstname><surname>Grob</surname><order>9</order></author><author><firstname>J.R.</firstname><surname>Hyngstrom</surname><order>10</order></author><author><firstname>John</firstname><surname>Wagstaff</surname><order>11</order></author><author><firstname>J.</firstname><surname>Chesney</surname><order>12</order></author><author><firstname>M.O.</firstname><surname>Butler</surname><order>13</order></author><author><firstname>O.</firstname><surname>Bechter</surname><order>14</order></author><author><firstname>I.</firstname><surname>M&#xE1;rquez-Rodas</surname><order>15</order></author><author><firstname>A.C.</firstname><surname>Pavlick</surname><order>16</order></author><author><firstname>P.</firstname><surname>Durani</surname><order>17</order></author><author><firstname>M. Pe</firstname><surname>Benito</surname><order>18</order></author><author><firstname>P.</firstname><surname>Wang</surname><order>19</order></author><author><firstname>M.A.</firstname><surname>Postow</surname><order>20</order></author><author><firstname>P.A.</firstname><surname>Ascierto</surname><order>21</order></author></authors><documents><document><filename>68590__33175__6be6801a6aa149bd95d76f4bbeb2c149.pdf</filename><originalFilename>68590.VOR.pdf</originalFilename><uploaded>2024-12-18T12:30:57.1331936</uploaded><type>Output</type><contentLength>1168153</contentLength><contentType>application/pdf</contentType><version>Version of Record</version><cronfaStatus>true</cronfaStatus><documentNotes>&#xA9; 2024 The Authors. 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spelling 2025-01-29T13:58:56.6044799 v2 68590 2024-12-18 Long-term outcomes among patients who respond within the first year to nivolumab plus ipilimumab or nivolumab monotherapy: A pooled analysis in 935 patients fdab5e9e2fe06c93d3ffa19c816bdcf6 John Wagstaff John Wagstaff true false 2024-12-18 MEDS Purpose: To investigate the predictive value of RECIST response within 3, 6, or 12 months on long-term survival, and explore differences between nivolumab+ipilimumab and nivolumab monotherapy, we analyzed pooled 5-year data of 935 responder and non-responder patients at various time points after treatment initiation in CheckMate 069, 066, and 067 studies. Patients and methods: Treatment-naive advanced melanoma patients received nivolumab+ipilimumab or nivolumab monotherapy. To decrease immortal time bias, 3-, 6-, or 12-month overall survival (OS) and progression-free survival (PFS) landmark analyses were performed. Association between characteristics and response was evaluated by univariate and multivariate analyses. Results: Response rates at any time were 58 % (239/409) for nivolumab+ipilimumab and 44 % (230/526) for nivolumab monotherapy. In 12-month landmark analyses, 5-year OS rates for responders versus non-responders were 82 % versus 40 % with nivolumab+ipilimumab (HR=0.23 [95 % CI, 0.15-0.35]) and 76 % versus 32 % with nivolumab monotherapy (HR=0.22 [95 % CI, 0.16-0.31]). PFS rates were 83 % versus 32 % and 69 % versus 46 %, respectively. Similar strong associations between response at 3 and 6 months and 5-year OS and PFS were also observed with more than 70 % of the responses observed in the first 3 months. Response rates correlated with baseline LDH and PD-L1 status by multivariate analysis but the association between response and long-term survival was maintained in landmark analyses even among patients with high LDH and low PD-L1 expression. Conclusion: Clinical response evaluated in the first months of therapy is a strong predictor of long-term survival, even in patients with poor prognostic biomarkers. Journal Article European Journal of Cancer 214 115119 Elsevier BV 0959-8049 1879-0852 Clinical response; Long-term survival; Advanced melanoma; Nivolumab; Ipilimumab; Prognostic factors 1 1 2025 2025-01-01 10.1016/j.ejca.2024.115119 COLLEGE NANME Medical School COLLEGE CODE MEDS Swansea University Another institution paid the OA fee The authors thank the patients and investigators who participated in the CheckMate 069, 066 and 067 trials. They acknowledge Ono Pharmaceutical Company, Ltd. (Osaka, Japan) for contributions to nivolumab development and Dako, an Agilent Technologies, Inc. company (Santa Clara, CA) for collaborative development of the PD-L1 immunohistochemistry 28–8 pharmDx assay. The authors thank Wim van Dijck from Bristol Myers Squibb for statistical contributions for the study, as well as Sandra Re and Jasmine Rizzo from Bristol Myers Squibb for medical oversight. Professional medical writing and editorial assistance were provided by Melissa Kirk, PhD, and Michele Salernitano at Ashfield MedComms, an Inizio Company, funded by Bristol Myers Squibb. M. Postow acknowledges support from the NIH/NCI Cancer Center Support Grant P30 CA008748. J. Wagstaff acknowledges grant support MSK P30 CA008748. J. Larkin acknowledges grant support from the National Institute for Health Research Royal Marsden-Institute of Cancer Research Biomedical Research Centre. This work was supported by Bristol Myers Squibb (Princeton, NJ). 2025-01-29T13:58:56.6044799 2024-12-18T12:19:36.4629088 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Biomedical Science C. Robert 1 G.V. Long 2 J. Larkin 3 J.D. Wolchok 4 J.C. Hassel 5 D. Schadendorf 6 F.S. Hodi 7 C. Lebbé 8 J.-J. Grob 9 J.R. Hyngstrom 10 John Wagstaff 11 J. Chesney 12 M.O. Butler 13 O. Bechter 14 I. Márquez-Rodas 15 A.C. Pavlick 16 P. Durani 17 M. Pe Benito 18 P. Wang 19 M.A. Postow 20 P.A. Ascierto 21 68590__33175__6be6801a6aa149bd95d76f4bbeb2c149.pdf 68590.VOR.pdf 2024-12-18T12:30:57.1331936 Output 1168153 application/pdf Version of Record true © 2024 The Authors. This is an open access article distributed under the terms of the Creative Commons CC-BY license. true eng http://creativecommons.org/licenses/by/4.0/
title Long-term outcomes among patients who respond within the first year to nivolumab plus ipilimumab or nivolumab monotherapy: A pooled analysis in 935 patients
spellingShingle Long-term outcomes among patients who respond within the first year to nivolumab plus ipilimumab or nivolumab monotherapy: A pooled analysis in 935 patients
John Wagstaff
title_short Long-term outcomes among patients who respond within the first year to nivolumab plus ipilimumab or nivolumab monotherapy: A pooled analysis in 935 patients
title_full Long-term outcomes among patients who respond within the first year to nivolumab plus ipilimumab or nivolumab monotherapy: A pooled analysis in 935 patients
title_fullStr Long-term outcomes among patients who respond within the first year to nivolumab plus ipilimumab or nivolumab monotherapy: A pooled analysis in 935 patients
title_full_unstemmed Long-term outcomes among patients who respond within the first year to nivolumab plus ipilimumab or nivolumab monotherapy: A pooled analysis in 935 patients
title_sort Long-term outcomes among patients who respond within the first year to nivolumab plus ipilimumab or nivolumab monotherapy: A pooled analysis in 935 patients
author_id_str_mv fdab5e9e2fe06c93d3ffa19c816bdcf6
author_id_fullname_str_mv fdab5e9e2fe06c93d3ffa19c816bdcf6_***_John Wagstaff
author John Wagstaff
author2 C. Robert
G.V. Long
J. Larkin
J.D. Wolchok
J.C. Hassel
D. Schadendorf
F.S. Hodi
C. Lebbé
J.-J. Grob
J.R. Hyngstrom
John Wagstaff
J. Chesney
M.O. Butler
O. Bechter
I. Márquez-Rodas
A.C. Pavlick
P. Durani
M. Pe Benito
P. Wang
M.A. Postow
P.A. Ascierto
format Journal article
container_title European Journal of Cancer
container_volume 214
container_start_page 115119
publishDate 2025
institution Swansea University
issn 0959-8049
1879-0852
doi_str_mv 10.1016/j.ejca.2024.115119
publisher Elsevier BV
college_str Faculty of Medicine, Health and Life Sciences
hierarchytype
hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Biomedical Science{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Biomedical Science
document_store_str 1
active_str 0
description Purpose: To investigate the predictive value of RECIST response within 3, 6, or 12 months on long-term survival, and explore differences between nivolumab+ipilimumab and nivolumab monotherapy, we analyzed pooled 5-year data of 935 responder and non-responder patients at various time points after treatment initiation in CheckMate 069, 066, and 067 studies. Patients and methods: Treatment-naive advanced melanoma patients received nivolumab+ipilimumab or nivolumab monotherapy. To decrease immortal time bias, 3-, 6-, or 12-month overall survival (OS) and progression-free survival (PFS) landmark analyses were performed. Association between characteristics and response was evaluated by univariate and multivariate analyses. Results: Response rates at any time were 58 % (239/409) for nivolumab+ipilimumab and 44 % (230/526) for nivolumab monotherapy. In 12-month landmark analyses, 5-year OS rates for responders versus non-responders were 82 % versus 40 % with nivolumab+ipilimumab (HR=0.23 [95 % CI, 0.15-0.35]) and 76 % versus 32 % with nivolumab monotherapy (HR=0.22 [95 % CI, 0.16-0.31]). PFS rates were 83 % versus 32 % and 69 % versus 46 %, respectively. Similar strong associations between response at 3 and 6 months and 5-year OS and PFS were also observed with more than 70 % of the responses observed in the first 3 months. Response rates correlated with baseline LDH and PD-L1 status by multivariate analysis but the association between response and long-term survival was maintained in landmark analyses even among patients with high LDH and low PD-L1 expression. Conclusion: Clinical response evaluated in the first months of therapy is a strong predictor of long-term survival, even in patients with poor prognostic biomarkers.
published_date 2025-01-01T05:24:41Z
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score 11.089572

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