Adjuvant immunotherapy in older patients with stage III and resected stage IV melanoma: Toxicity and recurrence-free survival outcomes from the Dutch melanoma treatment registry

被引：1

作者：

Ozkan, A. ^{[1
]}

Kapiteijn, E. ^{[1
]}

van den Bos, F. ^{[2
]}

Aarts, M. J. B. ^{[3
]}

van den Berkmortel, F. W. P. J. ^{[4
]}

Blank, C. U. ^{[1
,5
]}

Bloem, M. ^{[6
,7
,8
]}

Blokx, W. A. M. ^{[9
]}

Boers-Sonderen, M. J. ^{[10
]}

Bonenkamp, J. J. ^{[11
]}

van den Eertwegh, A. J. M. ^{[12
]}

de Groot, J. W. B. ^{[13
]}

Haanen, J. B. ^{[14
]}

Holtslag, C. E. ^{[1
]}

Hospers, G. A. P. ^{[15
]}

Piersma, D. ^{[16
]}

van Rijn, R. S. ^{[17
]}

Boer, A. M. Stevense-den ^{[18
]}

Suijkerbuijk, K. P. M. ^{[19
]}

van der Veldt, A. A. M. ^{[20
]}

Vreugdenhil, G. ^{[21
]}

Wouters, M. W. J. M. ^{[6
,7
,8
]}

Portielje, J. E. A. ^{[1
]}

de Glas, N. A. ^{[1
,22
,23
]}

机构：

[1] Leiden Univ, Med Ctr, Dept Med Oncol, Div Endocrinol, Albinusdreef 2, NL-2333ZA Leiden, Netherlands

[2] Leiden Univ, Med Ctr, Dept Gerontol & Geriatr, Albinusdreef 2, NL-2333ZA Leiden, Netherlands

[3] Maastricht Univ, Med Ctr, GROW Sch Oncol & Reprod, Dept Med Oncol, P Debyelaan 25, NL-6229 HX Maastricht, Netherlands

[4] Zuyderland Med Ctr, Dept Surg, Dr H Hoffpl 1, NL-6162 BG Sittard Geleen, Heerlen, Netherlands

[5] Netherlands Canc Inst, Dept Mol Oncol & Immunol, Plesmanlaan 121, NL-1066 CX Amsterdam, Netherlands

[6] Leiden Univ, Med Ctr, Dept Biomed Data Sci, Einthovenweg 20, NL-2333ZC Leiden, Netherlands

[7] Netherlands Canc Inst, Dept Surg, Plesmanlaan 121, NL-1066CX Amsterdam, Netherlands

[8] Dutch Inst Clin Auditing, Rijnsburgerweg 10, NL-2333 AA Leiden, Netherlands

[9] Univ Med Ctr Utrecht, Dept Pathol, Heidelberglaan 100, NL-3584CX Utrecht, Netherlands

[10] Radboud Univ Nijmegen, Med Ctr, Dept Med Oncol, Geert Grootepl Zuid 10, NL-6525GA Nijmegen, Netherlands

[11] Radboud Univ Nijmegen, Med Ctr, Dept Surg, Geert Grootepl Zuid 10, NL-6525GA Nijmegen, Netherlands

[12] Vrije Univ Amsterdam, Amsterdam UMC, Canc Ctr Amsterdam, Dept Med Oncol,Med Ctr, Boelelaan 1118, Amsterdam, Netherlands

[13] Isala, Isala Oncol Ctr, Dokter Heesweg 2, NL-8025 AB Zwolle, Netherlands

[14] Netherlands Canc Inst, Dept Pathol, Plesmanlaan 121, NL-1066CX Amsterdam, Netherlands

[15] Univ Groningen, Univ Med Ctr Groningen, Dept Med Oncol, Hanzepl 1, NL-9713GZ Groningen, Netherlands

[16] Med Spectrum Twente, Dept Internal Med, Koningspl 1, Enschede, Netherlands

[17] Med Ctr Leeuwarden, Dept Internal Med, Henri Dunantweg 2, Leeuwarden, Netherlands

[18] Amphia Hosp, Dept Internal Med, Molengracht 21, NL-4800 RK Breda, Netherlands

[19] Univ Utrecht, Univ Med Ctr Utrecht, Dept Radiol, Heidelberglaan 100, NL-3584CX Utrecht, Netherlands

[20] Erasmus MC, Dept Med Oncol & Radiol & Nucl Med, S Gravendijkwal 230, NL-3015CE Rotterdam, Netherlands

[21] Maxima Med Ctr, Dept Internal Med, Run 4600, NL-5504DB Eindhoven, Netherlands

[22] Helse Forde, Dept Med Oncol, Svanehaugvegen 2, N-6812 Helse Forde, Forde, Norway

[23] Albinusdreef 2,Postzone C7-R, NL-2300 RC Leiden, Netherlands

来源：

EUROPEAN JOURNAL OF CANCER | 2024年 / 212卷

关键词：

Oncology; Melanoma; Immune checkpoint inhibitors; Immune-related adverse events; Recurrence-free survival; DOUBLE-BLIND; PEMBROLIZUMAB; IPILIMUMAB; NIVOLUMAB;

D O I：

10.1016/j.ejca.2024.115056

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: Adjuvant anti-PD-1 therapy improves relapse free survival in stage III melanoma, but also leads to immune-related adverse events (irAEs). Older patients are of particular interest due to comorbidities and frailty, which may impact their ability to tolerate irAEs and benefit from anti-PD-1 therapy. This study aimed to explore associations between clinical parameters and the occurrence of grade >= 3 irAEs and recurrence-free survival (RFS) in older patients with radically resected stage III/IV cutaneous melanoma treated with adjuvant anti-PD-1 therapy. Methods: Patients aged >= 65 with resected stage III/IV cutaneous melanoma treated with adjuvant anti-PD-1 therapy between 2018 and 2022 were selected using real-world data from the nationwide Dutch Melanoma Treatment Registry (DMTR). A univariate and multivariable logistic regression was used to compare determinants of grade >= 3 irAEs, and univariate and multivariable Cox-proportional hazard models were fitted to identify factors influencing RFS. Results: The study included 885 patients, with 280 aged 75 and older. The incidence of grade >= 3 irAEs was 15.5 % in the 65-74 age group and 13.9 % in the >= 75 age group. No significant correlation was found between age and grade >= 3 irAEs. However, an increasing number of comorbidities was associated with a higher risk of grade >= 3 irAEs (multivariable analyses: OR 1.83, 95 % C.I. 0.99-3.40). The 1-year RFS rate of 80.0 % of this study was comparable to those reported in previous registration trials and real-world data. Having >= 3 comorbidities was significantly associated with a decrease in RFS (HR: 1.68, 95 % C.I. 1.15-2.44). Conclusion: Older patients had similar benefit of adjuvant immunotherapy compared to older subgroups in previous trials. However, patients with multiple comorbidities were at increased risk of grade >= 3 irAEs and had a lower RFS. This should be considered when deciding upon adjuvant treatment.

引用

页数：8

共 35 条

[1] Adjuvant nivolumab versus ipilimumab in resected stage IIIB-C and stage IV melanoma (CheckMate 238): 4-year results from a multicentre, double-blind, randomised, controlled, phase 3 trial [J].

Ascierto, Paolo A. ;

Del Vecchio, Michele ;

Mandala, Mario ;

Gogas, Helen ;

Arance, Ana M. ;

Dalle, Stephane ;

Cowey, C. Lance ;

Schenker, Michael ;

Grob, Jean-Jacques ;

Chiarion-Sileni, Vanna ;

Marquez-Rodas, Ivan ;

Butler, Marcus O. ;

Maio, Michele ;

Middleton, Mark R. ;

de la Cruz-Merino, Luis ;

Arenberger, Petr ;

Atkinson, Victoria ;

Hill, Andrew ;

Fecher, Leslie A. ;

Millward, Michael ;

Khushalani, Nikhil, I ;

Queirolo, Paola ;

Lobo, Maurice ;

de Pril, Veerle ;

Loffredo, John ;

Larkin, James ;

Weber, Jeffrey .

LANCET ONCOLOGY, 2020, 21 (11) :1465-1477

[2]

B.O.M. N-c op LinkedIn D., Adjuvant nivolumab bij stadium IIIb, IIIc of IV melanoom na volledige chirurgische resectie Inleiding

[3] Immunotherapy and targeted therapies in older patients with advanced melanoma; Young International Society of Geriatric Oncology review paper [J].

Bastiaannet, Esther ;

Battisti, Nicole ;

Loh, Kah Poh ;

de Glas, Nienke ;

Soto-Perez-de-Celis, Enrique ;

Baldini, Capucine ;

Kapiteijn, Ellen ;

Lichtman, Stuart .

JOURNAL OF GERIATRIC ONCOLOGY, 2019, 10 (03) :389-397

[4] Frailty and checkpoint inhibitor toxicity in older patients with melanoma [J].

Bruijnen, Cheryl P. ;

Koldenhof, Jose J. ;

Verheijden, Rik J. ;

van den Bos, Frederiek ;

Emmelot-Vonk, Marielle H. ;

Witteveen, Petronella O. ;

Suijkerbuijk, Karijn P. M. .

CANCER, 2022, 128 (14) :2746-2752

[5]

Carlino MS, 2021, LANCET, V398, P1002, DOI 10.1016/S0140-6736(21)01206-X

[6] Endocrine Toxicity of Cancer Immunotherapy Targeting Immune Checkpoints [J].

Chang, Lee-Shing ;

Barroso-Sousa, Romualdo ;

Tolaney, Sara M. ;

Hodi, F. Stephen ;

Kaiser, Ursula B. ;

Min, Le .

ENDOCRINE REVIEWS, 2019, 40 (01) :17-65

[7] Prediction of Other-Cause Mortality in Older Patients with Breast Cancer Using Comorbidity [J].

de Boer, Anna Z. ;

Bastiaannet, Esther ;

Putter, Hein ;

van de Mheen, Perla J. ;

Siesling, Sabine ;

de Munck, Linda ;

de Ligt, Kelly M. ;

Portielje, Johanneke E. A. ;

Liefers, Gerrit Jan ;

de Glas, Nienke A. .

CANCERS, 2021, 13 (07)

[8] Toxicity, Response and Survival in Older Patients with Metastatic Melanoma Treated with Checkpoint Inhibitors [J].

de Glas, Nienke A. ;

Bastiaannet, Esther ;

van den Bos, Frederiek ;

Mooijaart, Simon P. ;

van der Veldt, Astrid A. M. ;

Suijkerbuijk, Karlijn P. M. ;

Aarts, Maureen J. B. ;

van den Berkmortel, Franchette W. P. J. ;

Blank, Christian U. ;

Boers-Sonderen, Marye J. ;

van den Eertwegh, Alfonsus J. M. ;

de Groot, Jan-Willem B. ;

Haanen, John B. A. G. ;

Hospers, Geke A. P. ;

Jalving, Hilde ;

Piersma, Djura ;

van Rijn, Rozemarijn S. ;

ten Tije, Albert J. ;

Vreugdenhil, Gerard ;

Wouters, Michel W. J. M. ;

Portielje, Johanneke E. A. ;

Kapiteijn, Ellen W. .

CANCERS, 2021, 13 (11)

[9] Adjuvant treatment for melanoma in clinical practice - Trial versus reality [J].

de Meza, Melissa M. ;

Ismail, Rawa K. ;

Rauwerdink, Daan ;

van Not, Olivier J. ;

van Breeschoten, Jesper ;

Blokx, Willeke A. M. ;

de Boer, Anthonius ;

van Dartel, Maaike ;

Hilarius, Doranne L. ;

Ellebaek, Eva ;

Bonenkamp, Han J. ;

Blank, Christian U. ;

Aarts, Maureen J. B. ;

van Akkooi, Alexander C. J. ;

van den Berkmortel, Franchette W. P. J. ;

Boers-Sonderen, Marye J. ;

de Groot, Jan Willem B. ;

Haanen, John B. ;

Hospers, Geke A. P. ;

Kapiteijn, Ellen W. ;

Piersma, Djura ;

van Rijn, Roos S. ;

van der Veldt, Astrid A. M. ;

Vreugdenhil, Art ;

Westgeest, Hans M. ;

van den Eertwegh, Alfons J. M. ;

Suijkerbuijk, Karijn P. M. ;

Wouters, Michel W. J. M. .

EUROPEAN JOURNAL OF CANCER, 2021, 158 :234-245

[10] Adjuvant pembrolizumab versus placebo in resected stage III melanoma (EORTC 1325-MG/KEYNOTE-054): distant metastasis-free survival results from a double-blind, randomised, controlled, phase 3 trial [J].

Eggermont, Alexander M. M. ;

Blank, Christian U. ;

Mandala, Mario ;

Long, Georgina, V ;

Atkinson, Victoria G. ;

Dalle, Stephane ;

Haydon, Andrew M. ;

Meshcheryakov, Andrey ;

Khattak, Adnan ;

Carlino, Matteo S. ;

Sandhu, Shahneen ;

Larkin, James ;

Puig, Susana ;

Ascierto, Paolo A. ;

Rutkowski, Piotr ;

Schadendorf, Dirk ;

Koornstra, Rutger ;

Hernandez-Aya, Leonel ;

Giacomo, Anna Maria Di ;

van den Eertwegh, Alfonsus J. M. ;

Grob, Jean-Jacques ;

Gutzmer, Ralf ;

Jamal, Rahima ;

Lorigan, Paul C. ;

van Akkooi, Alexander C. J. ;

Krepler, Clemens ;

Ibrahim, Nageatte ;

Marreaud, Sandrine ;

Kicinski, Michal ;

Suciu, Stefan ;

Robert, Caroline .

LANCET ONCOLOGY, 2021, 22 (05) :643-654

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