Li Zhong1,2, Qing Wu1, Fuchun Chen3, Junjin Liu1, Xianhe Xie4,5. 1. Department of Oncology, The First Affiliated Hospital of Fujian Medical University, No. 20 Chazhong Road, Taijiang District, Fuzhou, 350005, China. 2. Department of Oncology, The Second Hospital of Longyan, Fujian, 364000, China. 3. Department of Gynecology, The First Hospital of Longyan, Fujian, 364000, China. 4. Department of Oncology, The First Affiliated Hospital of Fujian Medical University, No. 20 Chazhong Road, Taijiang District, Fuzhou, 350005, China. xiexianhe@fjmu.edu.cn. 5. Molecular Oncology Research Institute, First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, China. xiexianhe@fjmu.edu.cn.
Abstract
PURPOSE: This study was designed to investigate the correlation between immune-related adverse events (irAEs) of immune checkpoint inhibitors (ICIs) and corresponding efficacy, and to explore the potential of predicting the efficacy of ICIs via irAEs. METHODS: Electronic databases including PubMed, Embase, Cochrane Library, CNKI and Wanfang were applied to search for relevant studies. The primary endpoint was overall survival (OS) or progression-free survival (PFS), and the secondary endpoint was objective response rate (ORR). Stratification analyses were conducted according to the type of irAEs and ICIs, region of studies and primary tumors. Furthermore, statistical analyses were realized by means of RevMan 5.3 software. RESULTS: Altogether, 40 studies with 8,641 participants were enrolled, among which the incidence of irAEs ranged from 15.34 to 85.23% and the major sites reached out to skin, endocrine organ, gastrointestinal tract, liver and lung. The ORR, OS and PFS in irAE group were significantly higher than those in non-irAE group as per pooled analyses and stratification analyses. Importantly, patients with irAEs in skin, endocrine organ or gastrointestinal tract rather than in liver and lung were found to obtain survival benefits (p < 0.05). CONCLUSION: IrAEs, especially in skin, endocrine organ or gastrointestinal tract, triggered by ICIs indicate significant survival benefits.
PURPOSE: This study was designed to investigate the correlation between immune-related adverse events (irAEs) of immune checkpoint inhibitors (ICIs) and corresponding efficacy, and to explore the potential of predicting the efficacy of ICIs via irAEs. METHODS: Electronic databases including PubMed, Embase, Cochrane Library, CNKI and Wanfang were applied to search for relevant studies. The primary endpoint was overall survival (OS) or progression-free survival (PFS), and the secondary endpoint was objective response rate (ORR). Stratification analyses were conducted according to the type of irAEs and ICIs, region of studies and primary tumors. Furthermore, statistical analyses were realized by means of RevMan 5.3 software. RESULTS: Altogether, 40 studies with 8,641 participants were enrolled, among which the incidence of irAEs ranged from 15.34 to 85.23% and the major sites reached out to skin, endocrine organ, gastrointestinal tract, liver and lung. The ORR, OS and PFS in irAE group were significantly higher than those in non-irAE group as per pooled analyses and stratification analyses. Importantly, patients with irAEs in skin, endocrine organ or gastrointestinal tract rather than in liver and lung were found to obtain survival benefits (p < 0.05). CONCLUSION: IrAEs, especially in skin, endocrine organ or gastrointestinal tract, triggered by ICIs indicate significant survival benefits.
Authors: Caroline Robert; Georgina V Long; Benjamin Brady; Caroline Dutriaux; Michele Maio; Laurent Mortier; Jessica C Hassel; Piotr Rutkowski; Catriona McNeil; Ewa Kalinka-Warzocha; Kerry J Savage; Micaela M Hernberg; Celeste Lebbé; Julie Charles; Catalin Mihalcioiu; Vanna Chiarion-Sileni; Cornelia Mauch; Francesco Cognetti; Ana Arance; Henrik Schmidt; Dirk Schadendorf; Helen Gogas; Lotta Lundgren-Eriksson; Christine Horak; Brian Sharkey; Ian M Waxman; Victoria Atkinson; Paolo A Ascierto Journal: N Engl J Med Date: 2014-11-16 Impact factor: 91.245
Authors: Michael J Overman; Ray McDermott; Joseph L Leach; Sara Lonardi; Heinz-Josef Lenz; Michael A Morse; Jayesh Desai; Andrew Hill; Michael Axelson; Rebecca A Moss; Monica V Goldberg; Z Alexander Cao; Jean-Marie Ledeine; Gregory A Maglinte; Scott Kopetz; Thierry André Journal: Lancet Oncol Date: 2017-07-19 Impact factor: 41.316
Authors: Joaquim Bellmunt; Ronald de Wit; David J Vaughn; Yves Fradet; Jae-Lyun Lee; Lawrence Fong; Nicholas J Vogelzang; Miguel A Climent; Daniel P Petrylak; Toni K Choueiri; Andrea Necchi; Winald Gerritsen; Howard Gurney; David I Quinn; Stéphane Culine; Cora N Sternberg; Yabing Mai; Christian H Poehlein; Rodolfo F Perini; Dean F Bajorin Journal: N Engl J Med Date: 2017-02-17 Impact factor: 91.245
Authors: Caroline Robert; Jacob Schachter; Georgina V Long; Ana Arance; Jean Jacques Grob; Laurent Mortier; Adil Daud; Matteo S Carlino; Catriona McNeil; Michal Lotem; James Larkin; Paul Lorigan; Bart Neyns; Christian U Blank; Omid Hamid; Christine Mateus; Ronnie Shapira-Frommer; Michele Kosh; Honghong Zhou; Nageatte Ibrahim; Scot Ebbinghaus; Antoni Ribas Journal: N Engl J Med Date: 2015-04-19 Impact factor: 91.245
Authors: Dung T Le; Jennifer N Durham; Kellie N Smith; Hao Wang; Bjarne R Bartlett; Laveet K Aulakh; Steve Lu; Holly Kemberling; Cara Wilt; Brandon S Luber; Fay Wong; Nilofer S Azad; Agnieszka A Rucki; Dan Laheru; Ross Donehower; Atif Zaheer; George A Fisher; Todd S Crocenzi; James J Lee; Tim F Greten; Austin G Duffy; Kristen K Ciombor; Aleksandra D Eyring; Bao H Lam; Andrew Joe; S Peter Kang; Matthias Holdhoff; Ludmila Danilova; Leslie Cope; Christian Meyer; Shibin Zhou; Richard M Goldberg; Deborah K Armstrong; Katherine M Bever; Amanda N Fader; Janis Taube; Franck Housseau; David Spetzler; Nianqing Xiao; Drew M Pardoll; Nickolas Papadopoulos; Kenneth W Kinzler; James R Eshleman; Bert Vogelstein; Robert A Anders; Luis A Diaz Journal: Science Date: 2017-06-08 Impact factor: 47.728
Authors: Martin Reck; Delvys Rodríguez-Abreu; Andrew G Robinson; Rina Hui; Tibor Csőszi; Andrea Fülöp; Maya Gottfried; Nir Peled; Ali Tafreshi; Sinead Cuffe; Mary O'Brien; Suman Rao; Katsuyuki Hotta; Melanie A Leiby; Gregory M Lubiniecki; Yue Shentu; Reshma Rangwala; Julie R Brahmer Journal: N Engl J Med Date: 2016-10-08 Impact factor: 91.245
Authors: Charles S Fuchs; Toshihiko Doi; Raymond W Jang; Kei Muro; Taroh Satoh; Manuela Machado; Weijing Sun; Shadia I Jalal; Manish A Shah; Jean-Phillipe Metges; Marcelo Garrido; Talia Golan; Mario Mandala; Zev A Wainberg; Daniel V Catenacci; Atsushi Ohtsu; Kohei Shitara; Ravit Geva; Jonathan Bleeker; Andrew H Ko; Geoffrey Ku; Philip Philip; Peter C Enzinger; Yung-Jue Bang; Diane Levitan; Jiangdian Wang; Minori Rosales; Rita P Dalal; Harry H Yoon Journal: JAMA Oncol Date: 2018-05-10 Impact factor: 31.777
Authors: Robert J Motzer; Bernard Escudier; David F McDermott; Saby George; Hans J Hammers; Sandhya Srinivas; Scott S Tykodi; Jeffrey A Sosman; Giuseppe Procopio; Elizabeth R Plimack; Daniel Castellano; Toni K Choueiri; Howard Gurney; Frede Donskov; Petri Bono; John Wagstaff; Thomas C Gauler; Takeshi Ueda; Yoshihiko Tomita; Fabio A Schutz; Christian Kollmannsberger; James Larkin; Alain Ravaud; Jason S Simon; Li-An Xu; Ian M Waxman; Padmanee Sharma Journal: N Engl J Med Date: 2015-09-25 Impact factor: 91.245
Authors: Robert L Ferris; George Blumenschein; Jerome Fayette; Joel Guigay; A Dimitrios Colevas; Lisa Licitra; Kevin Harrington; Stefan Kasper; Everett E Vokes; Caroline Even; Francis Worden; Nabil F Saba; Lara C Iglesias Docampo; Robert Haddad; Tamara Rordorf; Naomi Kiyota; Makoto Tahara; Manish Monga; Mark Lynch; William J Geese; Justin Kopit; James W Shaw; Maura L Gillison Journal: N Engl J Med Date: 2016-10-08 Impact factor: 91.245