Efficacy and safety of PD-1/PD-L1 inhibitors in patients with Merkel Cell Carcinoma: a systematic review and Meta-analysis

被引:1
作者
de Moraes, Francisco Cezar Aquino [1 ]
Kreuz, Michele [2 ]
de Lara, Isabella Christina Amaral [3 ]
Lobo, Artur de Oliveira Macena [4 ]
Burbano, Rommel Mario Rodriguez [1 ,5 ]
机构
[1] Fed Univ Para, R Augusto Correa 01, BR-66075110 Belem, PA, Brazil
[2] Univ Luterana Brasil, BR-92425020 Canoas, RS, Brazil
[3] Cesumar Univ, BR-87050900 Maringa, PR, Brazil
[4] Univ Fed Pernambuco, BR-50670901 Recife, PE, Brazil
[5] Ophir Loyola Hosp, BR-66063240 Belem, PA, Brazil
关键词
Merkel cell carcinoma; Skin cancer; PD-1/PD-L1; inhibitors; Meta-analysis; PD-1; BLOCKADE; CHEMOTHERAPY; RESISTANCE; OUTCOMES; THERAPY;
D O I
10.1186/s12885-024-13129-1
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
BackgroundMerkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine skin cancer characterized by high rates of metastasis. Emerging evidence suggests that PD-L1/PD1 blockade holds promise as a therapeutic option for MCC. However, the efficacy and safety of this approach in treating MCC remain incompletely understood. This systematic review and meta-analysis aims to analyze the efficacy and safety of PD-1/PD-L1 blockade for patients with MCC.MethodsPubMed, Cochrane, and Embase were searched for studies evaluating patients with MCC undergoing PD-1/PD-L1 treatment. The estimated outcomes were overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (TRAEs). We performed the meta-analysis using RStudio v4.4.2 software.ResultsA total of 14 reports of 13 different studies encompassing 615 patients were included. The median age ranged from 64 to 77 years. Median follow-up ranged from 7.9 months to 59.3 months. Pooled OS rates at 24 and 36 months were 65.05% (95% CI 44.04-81.49) and 59.58% (95% CI 39.62-76.81), respectively, while pooled PFS rates at 6, 12, and 36 months were 51.78% (95% CI 37.83-65.45), 46.12% (95% CI 29.44-63.72), and 28.73% (95% CI 16.57-45.02), in the same order. DCR proportion was 61.65% (95% CI 54.85-68.03) and ORR was 53.79% (95% CI 47.80-59.68). The frequency of TRAEs of any grade was 61.72% (95% CI 45.75-75.51) and for TRAEs of grade >= 3 was 17.60% (95% CI 12.28 to 24.57).ConclusionsThis systematic review and meta-analysis revealed that patients with MCC undergoing treatment with PD-1/PDL-1 showed durable responses with continuous and clinically meaningful survival outcomes.
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页数:13
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共 53 条
[21]   Measuring inconsistency in meta-analyses [J].
Higgins, JPT ;
Thompson, SG ;
Deeks, JJ ;
Altman, DG .
BMJ-BRITISH MEDICAL JOURNAL, 2003, 327 (7414) :557-560
[22]   Immune-related adverse events: a retrospective look into the future of oncology in the intensive care unit [J].
Joseph, Adrien ;
Simonaggio, Audrey ;
Stoclin, Annabelle ;
Vieillard-Baron, Antoine ;
Geri, Guillaume ;
Oudard, Stephane ;
Michot, Jean-Marie ;
Lambotte, Olivier ;
Azoulay, Elie ;
Lemiale, Virginie .
ANNALS OF INTENSIVE CARE, 2020, 10 (01)
[23]   T cell exclusion, immune privilege, and the tumor microenvironment [J].
Joyce, Johanna A. ;
Fearon, Douglas T. .
SCIENCE, 2015, 348 (6230) :74-80
[24]   Durable remission after rechallenge with ipilimumab and nivolumab in metastatic Merkel cell carcinoma refractory to avelumab: Any role for sequential immunotherapy? [J].
Khaddour, Karam ;
Rosman, Ilana S. ;
Dehdashti, Farrokh ;
Ansstas, George .
JOURNAL OF DERMATOLOGY, 2021, 48 (02) :E80-E81
[25]   Combined nivolumab and ipilimumab with or without stereotactic body radiation therapy for advanced Merkel cell carcinoma: a randomised, open label, phase 2 trial [J].
Kim, Sungjune ;
Wuthrick, Evan ;
Blakaj, Dukagjin ;
Eroglu, Zeynep ;
Verschraegen, Claire ;
Thapa, Ram ;
Mills, Matthew ;
Dibs, Khaled ;
Liveringhouse, Casey ;
Russell, Jeffery ;
Caudell, Jimmy J. ;
Tarhini, Ahmad ;
Markowitz, Joseph ;
Kendra, Kari ;
Wu, Richard ;
Chen, Dung-Tsa ;
Berglund, Anders ;
Michael, Lauren ;
Aoki, Mia ;
Wang, Min-Hsuan ;
Hamaidi, Imene ;
Cheng, Pingyan ;
de la Iglesia, Janis ;
Slebos, Robbert J. ;
Chung, Christine H. ;
Knepper, Todd C. ;
Moran-Segura, Carlos M. ;
Nguyen, Jonathan, V ;
Perez, Bradford A. ;
Rose, Trevor ;
Harrison, Louis ;
Messina, Jane L. ;
Sondak, Vernon K. ;
Tsai, Kenneth Y. ;
Khushalani, Nikhil, I ;
Brohl, Andrew S. .
LANCET, 2022, 400 (10357) :1008-1019
[26]   Diagnosis and treatment of Merkel Cell Carcinoma. European consensus-based interdisciplinary guideline [J].
Lebbe, Celeste ;
Becker, Juergen C. ;
Grob, Jean-Jacques ;
Malvehy, Josep ;
del Marmol, Veronique ;
Pehamberger, Hubert ;
Peris, Ketty ;
Saiag, Philippe ;
Middleton, Mark R. ;
Bastholt, Lars ;
Testori, Alessandro ;
Stratigos, Alexander ;
Garbe, Claus .
EUROPEAN JOURNAL OF CANCER, 2015, 51 (16) :2396-2403
[27]   Avelumab for advanced Merkel cell carcinoma in the Netherlands: a real-world cohort [J].
Levy, Sonja ;
Aarts, Maureen J. B. ;
Eskens, Ferry A. L. M. ;
Keymeulen, Kristien B. M., I ;
Been, Lukas B. ;
Grunhagen, Dirk ;
van Akkooi, Alexander ;
Jalving, Mathilde ;
Tesselaar, Margot E. T. .
JOURNAL FOR IMMUNOTHERAPY OF CANCER, 2020, 8 (02)
[28]   PD-L1 Expression in the Merkel Cell Carcinoma Microenvironment: Association with Inflammation, Merkel Cell Polyomavirus, and Overall Survival [J].
Lipson, Evan J. ;
Vincent, Jeremy G. ;
Loyo, Myriam ;
Kagohara, Luciane T. ;
Luber, Brandon S. ;
Wang, Hao ;
Xu, Haiying ;
Nayar, Suresh K. ;
Wang, Timothy S. ;
Sidransky, David ;
Anders, Robert A. ;
Topalian, Suzanne L. ;
Taube, Janis M. .
CANCER IMMUNOLOGY RESEARCH, 2013, 1 (01) :54-63
[29]   Evidence for a Role of the PD-1:PD-L1 Pathway in Immune Resistance of HPV-Associated Head and Neck Squamous Cell Carcinoma [J].
Lyford-Pike, Sofia ;
Peng, Shiwen ;
Young, Geoffrey D. ;
Taube, Janis M. ;
Westra, William H. ;
Akpeng, Belinda ;
Bruno, Tullia C. ;
Richmon, Jeremy D. ;
Wang, Hao ;
Bishop, Justin A. ;
Chen, Lieping ;
Drake, Charles G. ;
Topalian, Suzanne L. ;
Pardoll, Drew M. ;
Pai, Sara I. .
CANCER RESEARCH, 2013, 73 (06) :1733-1741
[30]   Anti-PD1-based neoadjuvant therapy in resectable stage III or IV melanoma patients: A systematic review and meta-analysis [J].
Madeira, T. M. ;
Moraes, F. Cezar A. ;
Priantti, J. N. ;
Santiago, E. Moises de Lima ;
Ribeiro, M. F. ;
Vilbert, M. Silveira .
ANNALS OF ONCOLOGY, 2023, 34 :S661-S661