Cong Chen1,2, Fan Zhang1,2, Ning Zhou2,3, Yan-Mei Gu1,2, Ya-Ting Zhang1,2, Yi-Di He1,2, Ling Wang1,2, Lu-Xi Yang1,4, Yang Zhao1,4, Yu-Min Li1,2,4. 1. Lanzhou University Second Hospital, Lanzhou, Gansu, China. 2. The Second Clinical Medical College of Lanzhou University, Lanzhou, Gansu, China. 3. The First People's Hospital of Lanzhou City, Lanzhou, Gansu, China. 4. Key Laboratory of Digestive System Tumors of Gansu Province, Lanzhou, Gansu, China.
Abstract
Background: Immune checkpoint inhibitors (ICI) have shown promising prospects in gastroesophageal junction (G/GEJ) cancer immunotherapy, many clinical trials have been carried out. Objective: To evaluate the efficacy and safety of ICI in G/GEJ cancer. Methods: The published English articles of PubMed, Cochrane Library, Embase, Web of Science were searched up to 30/09/2018. The efficacy and safety of ICI were analyzed by meta-analysis. Results: A total of 2003 patients from nine clinical trials were included. Anti-PD-1 treatment improved the 12-month, 18-month overall survival (OS) rate (RR, 1.79 p = 0.013; 2.20 p = 0.011) and prolonged the duration of response (DOR) (MSR, 3.27 p < 0.001). The objective response rate (ORR) in PD-L1+ patients was greater than PD-L1- (RR, 4.31 p < 0.001). Microsatellite instability-high (MSI-H) patients had higher ORR and disease control rate (DCR) than microsatellite stability (MSS) (RR, 3.40 p< 0.001; 2.26 p= 0.001). The most common grade ≥3 treatment-related adverse events (TRAEs) were fatigue, aspartate aminotransferase increased, hepatitis, pneumonitis, colitis, hypopituitarism. The TRAE incidence of anti-PD-1/PD-L1 was less than chemotherapy (TRAE RR = 0.64 p< 0.001; ≥3 TRAE RR = 0.37 p < 0.001). The incidence of ≥3 TRAEs of anti-PD-1/PD-L1 treatment was less than that of anti-CTLA-4 (11.7% vs 43.9%). Conclusions: ICI treatment could improve some but not all survival endpoints to advanced or metastatic G/GEJ cancer patients suggesting modest benefit and less adverse reactions. Anti-PD-1/PD-L1 therapy was more effective to PD-L1+, MSI-H, EBV+, or high tumor mutational burden patients.
Background: Immune checkpoint inhibitors (ICI) have shown promising prospects in gastroesophageal junction (G/GEJ) cancer immunotherapy, many clinical trials have been carried out. Objective: To evaluate the efficacy and safety of ICI in G/GEJ cancer. Methods: The published English articles of PubMed, Cochrane Library, Embase, Web of Science were searched up to 30/09/2018. The efficacy and safety of ICI were analyzed by meta-analysis. Results: A total of 2003 patients from nine clinical trials were included. Anti-PD-1 treatment improved the 12-month, 18-month overall survival (OS) rate (RR, 1.79 p = 0.013; 2.20 p = 0.011) and prolonged the duration of response (DOR) (MSR, 3.27 p < 0.001). The objective response rate (ORR) in PD-L1+ patients was greater than PD-L1- (RR, 4.31 p < 0.001). Microsatellite instability-high (MSI-H) patients had higher ORR and disease control rate (DCR) than microsatellite stability (MSS) (RR, 3.40 p< 0.001; 2.26 p= 0.001). The most common grade ≥3 treatment-related adverse events (TRAEs) were fatigue, aspartate aminotransferase increased, hepatitis, pneumonitis, colitis, hypopituitarism. The TRAE incidence of anti-PD-1/PD-L1 was less than chemotherapy (TRAE RR = 0.64 p< 0.001; ≥3 TRAE RR = 0.37 p < 0.001). The incidence of ≥3 TRAEs of anti-PD-1/PD-L1 treatment was less than that of anti-CTLA-4 (11.7% vs 43.9%). Conclusions: ICI treatment could improve some but not all survival endpoints to advanced or metastatic G/GEJ cancerpatients suggesting modest benefit and less adverse reactions. Anti-PD-1/PD-L1 therapy was more effective to PD-L1+, MSI-H, EBV+, or high tumor mutational burden patients.
Authors: Christy Ralph; Eyad Elkord; Deborah J Burt; Jackie F O'Dwyer; Eric B Austin; Peter L Stern; Robert E Hawkins; Fiona C Thistlethwaite Journal: Clin Cancer Res Date: 2010-02-23 Impact factor: 12.531
Authors: Hugo E R Ford; Andrea Marshall; John A Bridgewater; Tobias Janowitz; Fareeda Y Coxon; Jonathan Wadsley; Wasat Mansoor; David Fyfe; Srinivasan Madhusudan; Gary W Middleton; Daniel Swinson; Stephen Falk; Ian Chau; David Cunningham; Paula Kareclas; Natalie Cook; Jane M Blazeby; Janet A Dunn Journal: Lancet Oncol Date: 2013-12-10 Impact factor: 41.316
Authors: Charles S Fuchs; Jiri Tomasek; Cho Jae Yong; Filip Dumitru; Rodolfo Passalacqua; Chanchal Goswami; Howard Safran; Lucas Vieira Dos Santos; Giuseppe Aprile; David R Ferry; Bohuslav Melichar; Mustapha Tehfe; Eldar Topuzov; John Raymond Zalcberg; Ian Chau; William Campbell; Choondal Sivanandan; Joanna Pikiel; Minori Koshiji; Yanzhi Hsu; Astra M Liepa; Ling Gao; Jonathan D Schwartz; Josep Tabernero Journal: Lancet Date: 2013-10-03 Impact factor: 79.321
Authors: Kathryn E Cole; Quan P Ly; Michael A Hollingsworth; Jesse L Cox; Kurt W Fisher; James C Padussis; Jason M Foster; Luciano M Vargas; James E Talmadge Journal: Int Immunopharmacol Date: 2022-02-21 Impact factor: 4.932
Authors: M Santero; J Pérez-Bracchiglione; R Acosta-Dighero; A G Meade; A Antequera; A Auladell-Rispau; M J Quintana; C Requeijo; G Rodríguez-Grijalva; K Salas-Gama; R Dorantes-Romandia; J Salazar; I Solà; G Urrútia; X Bonfill Cosp Journal: BMC Cancer Date: 2021-06-16 Impact factor: 4.430