Adverse Events in Anti-PD-1-Treated Adjuvant and First-Line Advanced Melanoma Patients

被引：1

作者：

Rauwerdink, Daan Jan Willem ^{[1
]}

van Not, Olivier ^{[1
,2
]}

de Meza, Melissa ^{[3
]}

van Doorn, Remco ^{[1
]}

van der Hage, Jos ^{[4
]}

van den Eertwegh, A. J. M. ^{[5
]}

Haanen, John B. ^{[6
,7
,8
]}

Aarts, Maureen J. B. ^{[9
]}

van den Berkmortel, Franchette W. P. J. ^{[10
]}

Blank, Christiaan U. ^{[6
,7
,8
]}

Boers-Sonderen, Marye J. ^{[11
]}

de Groot, Jan Willem B. ^{[12
]}

Hospers, Geke A. P. ^{[13
]}

Piersma, Djura ^{[14
]}

van Rijn, Rozemarijn S. ^{[15
]}

Boer, A. M. Stevense-den ^{[16
]}

van der Veldt, Astrid A. M. ^{[17
]}

Vreugdenhil, Gerard ^{[18
]}

Wouters, Michel W. J. M. ^{[2
,4
,19
]}

Suijkerbuijk, Karijn P. M. ^{[20
]}

Kapiteijn, Ellen ^{[8
]}

机构：

[1] Leiden Univ, Med Ctr, Dept Dermatol, Albinusdreef 2,POB 9600, NL-2300 RC Leiden, Netherlands

[2] Dutch Inst Clin Auditing, Sci Bur, Rijnsburgerweg 10, NL-2333 AA Leiden, Netherlands

[3] Leiden Univ, Med Ctr, Dept Ear Nose Throat ENT, Albinusdreef 2,POB 9600, NL-2300 RC Leiden, Netherlands

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

[5] Vrije Univ Amsterdam Med Ctr, Canc Ctr Amsterdam, Dept Med Oncol, Amsterdam UMC, NL-1081 HZ Amsterdam, Netherlands

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

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

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

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

[10] Zuyderland Med Ctr Sittard, Dept Med Oncol, Dr H van der Hoffpl 1, NL-6162 BG Geleen, Netherlands

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

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

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

[14] Med Spectrum Twente, Dept Internal Med, Koningsp 1, NL-7512 KZ Enschede, Netherlands

[15] Med Ctr Leeuwarden, Dept Internal Med, Henri Dunantweg 2, NL-8934 AD Leeuwarden, Netherlands

[16] Amphia Hosp, Dept Internal Med, Molengracht 21, NL-4818 CK Breda, Netherlands

[17] Erasmus MC, Dept Med Oncol & Radiol & Nucl Med, Sgravendijkwal 230, NL-3015 CE Rotterdam, Netherlands

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

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

[20] Univ Utrecht, Univ Med Ctr Utrecht, Dept Med Oncol, Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands

来源：

CANCERS | 2024年 / 16卷 / 15期

关键词：

melanoma; immune checkpoint inhibitors; side-effects; NIVOLUMAB; IPILIMUMAB; CANCER; IMMUNOTHERAPY;

D O I：

10.3390/cancers16152656

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Introduction: The difference in incidence and severity of anti-PD-1 therapy-related adverse events (irAEs) between adjuvant and advanced treated melanoma patients remains unclear, as no head-to-head studies have compared these groups. Methods: This multi-center cohort study analyzed melanoma patients treated with anti-PD-1 in adjuvant or advanced settings between 2015 and 2021. Comorbidities and ECOG performance status were assessed before treatment, and grade III-IV irAEs were monitored during treatment. Univariate and multivariate regression analyses were conducted to identify factors associated with irAE development. Results: A total of 1465 advanced melanoma patients and 908 resected melanoma patients received anti-PD-1 therapy. Adjuvant-treated patients were younger, with a median age of 63 years compared to 69 years in the advanced group (p < 0.01), and had a better ECOG performance status (p < 0.01). Comorbidities were seen more frequently in advanced melanoma patients than in those receiving adjuvant treatment, 76% versus 68% (p < 0.01). Grade III-IV irAEs occurred in 214 (15%) advanced treated patients and in 119 (13%) adjuvant-treated patients. Multivariate analysis showed an increased risk of severe irAE development with the presence of any comorbidity (adjusted OR 1.22, 95% CI 1.02-1.44) and ECOG status greater than 1 (adjusted OR 2.00, 95% CI 1.20-3.32). Adjuvant therapy was not associated with an increased risk of irAE development compared to advanced treatment (adjusted OR 0.95, 95% CI 0.74-1.21) after correcting for comorbidities and ECOG performance score. Anti-PD-1 therapy was halted due to toxicity (any grade irAE) more often in the adjuvant setting than in the advanced setting, 20% versus 15% (p < 0.01). Conclusions: Higher ECOG performance status and presence of any comorbidity were independently associated with an increased risk of Grade III-IV irAE in adjuvant and advanced treated melanoma patients. Patients treated in the adjuvant setting did not have an increased risk of developing severe irAEs compared to advanced melanoma patients. These findings are of clinical significance in consulting patients for adjuvant anti-PD-1 treatment.

引用

页数：13

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