Assessment of the Clinical Trials Safety Profile of PD-1/PD-L1 Inhibitors Among Patients With Cancer: An Updated Systematic Review and Meta-Analysis

Tian, Yuan; Huang, Alan; Yang, Yue; Dang, Qi; Wen, Qing; Wang, Linlin; Sun, Yeping

doi:10.3389/fonc.2021.662392

Cited by 3 publications

(3 citation statements)

References 74 publications

(414 reference statements)

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“…Basic characteristics of 86 clinical trials included in the study were extracted and shown in Table 1 [ 5 ], [ 22 – 25 ], [ 26 – 30 ], [ 31 – 35 ], [ 36 – 40 ], [ 41 – 45 ], [ 46 – 50 ], [ 51 – 55 ], [ 56 – 60 ], [ 61 – 65 ], [ 66 – 70 ], [ 71 – 75 ], [ 76 – 80 ], [ 81 – 85 ], [ 86 – 90 ], [ 91 – 95 ], [ 96 – 110 ], [ 111 – 115 ], [ 116 , 117 ]. 6 clinical trials, including KEYNOTE-021 [ 27 , 28 ], KEYNOTE-189 [ 40 – 42 ], CheckMate 227 [ 47 , 48 ], JAVELIN Renal 101 [ 51 , 52 ], KEYNOTE-042 [ 61 , 62 ], and CheckMate 067 [ 114 – 117 ], were repeatedly reported multiple times by different reporters, and only one with the detailed data could be selected for the final analyses.…”

Section: Resultsmentioning

confidence: 99%

“…On the basis of research into the mechanisms of immune escape, PD-1 or PD-L1 inhibitors have reshaped the therapy landscape for cancer by activating the immune system, while also gradually reporting plenty of treatment-related side effects [3]. Although the association between some adverse events and PD-1 or PD-L1 inhibitors has been extensively examined and documented [4][5][6][7][8][9], many toxicities remain unexplored, including skin toxicities [3].…”

Section: Introductionmentioning

confidence: 99%

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Risk of Rash in PD-1 or PD-L1-Related Cancer Clinical Trials: A Systematic Review and Meta-Analysis

Tian¹,

Zhang

Dang

et al. 2022

Journal of Oncology

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Background. Given that immune-related rash was the most frequently reported PD-1 or PD-L1-related skin toxicity, this systematic review and meta-analysis were conducted to elucidate its incidence risk. Methods. The meta-analysis was carried out according to the PRISMA guidelines. The random effect model was used in the process of all analyses. Skin rash of all grades and grades 3–5 were calculated and gathered in the final comprehensive analyses. Results. The study included 86 clinical trials classified into 15 groups. Compared with chemotherapy, PD-1 or PD-L1 inhibitors significantly strengthened the risk of developing rash across all grades (OR = 1.66, 95% CI: [1.31, 2.11]; p < 0.0001 ). This trend was significantly stronger when the control group was placebo (OR = 2.62, 95% CI: [1.88, 3.65]; p < 0.00001 ). Similar results were observed when PD-1 or PD-L1 inhibitors were given together with chemotherapy (OR = 1.87, 95% CI: [1.59, 2.20]; p < 0.00001 ), even in patients with grades 3–5. As with other combination therapies, the risk of developing rash for all grades was enhanced when PD-1 or PD-L1 was given together with chemotherapy as the second-line option (OR = 2.98, 95% CI: [1.87, 4.75]; p = 0.05 ). No statistically significant differences could be found in skin rash between the PD-1 and PD-L1-related subgroups. Conclusion. Whether PD-1 or PD-L1 inhibitors were given alone or together with others, the risk of developing rash would be enhanced. Furthermore, the risk of developing rash appeared to be higher when PD-1 or PD-L1 inhibitors together with other antitumor drugs were given as the second-line options. No statistically significant results of developing rash between PD-1 and PD-L1 subgroups were obtained owing to the participation of PD-1 or PD-L1 inhibitors.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Risk of Rash in PD-1 or PD-L1-Related Cancer Clinical Trials: A Systematic Review and Meta-Analysis

Tian¹,

Zhang

Dang

et al. 2022

Journal of Oncology

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“…Among all immune checkpoints, the PD-1/PD-L1 signaling pathway has received increasing attention due to its proven outstanding effectiveness as an immune therapeutic target in a wide range of tumors, including bladder cancer, lung cancer, and pancreatic cancer [6][7][8]. However, the response to anti-PD-1/PD-L1 therapy differs among different malignancies and patients, and multiple mechanisms have been found to hinder tumor immunity during tumorigenesis [9][10][11]. This finding urges current researchers to evaluate the underlying mechanisms by which the PD-1/PD-L1 pathway is regulated in tumorigenesis.…”

Section: Introductionmentioning

confidence: 99%

The role of lncRNAs and circRNAs in the PD-1/PD-L1 pathway in cancer immunotherapy

et al. 2021

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Cancer immunotherapy has recently shown promising antitumor effects in various types of tumors. Among all immune checkpoints, the PD-1/PD-L1 pathway plays an important role in the immune evasion of tumor cells, making it a potent target in antitumor immunity. Accordingly, antibodies targeting the PD-1/PD-L1 pathway have been developed to attack tumor cells; however, resistance to immune therapy remains to be solved. Hence, identification of the underlying modulators of the PD-1/PD-L1 pathway is of significant importance to understand the mechanisms of antitumor immunotherapy. Long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) have been identified to regulate the PD-1/PD-L1 pathway, leading to participation in the immune response and immunotherapy. Therefore, this review focuses on the functions of lncRNAs and circRNAs in regulation of the PD-1/PD-L1 axis in tumorigenesis and tumor progression. We hope this review will stimulate research to supply more precise and effective cancer immune checkpoint therapies for a large number of tumors.

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Does it fit in your pocket? economic burden of PD-1 inhibitors' toxicity in the supplementary health system: evidence from Brazil

Duarte

Veiga

et al. 2023

BMC Health Serv Res

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Background A full understanding of the economic burden associated with treatment-related adverse events (AEs) can aid estimates of the incremental costs associated with incorporating new technologies and support cost-effective economic modeling in Brazil. In this context, the main objective of this work was to evaluate in a real-life database: (i) the direct medical cost of monitoring the occurrence of AEs (CMO); (ii) the direct medical cost of managing an identified AE (CMN); and (iii) the total direct medical cost of monitoring and managing AEs (TMC), in quarterly periods from 0 to 24 months of the monitoring of cancer patients who used a PD-1 inhibitor from the perspective of the supplementary health system in Brazil. Methods This study was conducted from the supplementary health system (SSS) perspective and followed the methodological guidelines related to cost-of-illness studies. A bottom-up (person-based) approach was used to assess the use of health resources to monitor and manage AEs during the use of PD-1 inhibitors, which made it possible to capture differences in the mean frequency of the use of health services with stratification results for different subgroups. As the Brazilian SSS is complex, asymmetric, and fragmented, this study used information from different sources. The methodology was divided into three parts: (i) Data Source: clinical management of AEs; (ii) Microcosting: management of the economic burden of AEs; (iii) Statistical analysis: stratification of results for different subgroups. Results Analysis of the economic burden of toxicity showed higher CMO costs than CMN in all the periods analyzed. In general, for every BRL 100 on average invested in the TMC of AEs, BRL 95 are used to monitor the occurrence of the AE and only BRL 5 to manage an identified AE. This work also showed that the sociodemographic characteristics of patients, the journey of oncological treatment, and the toxicity profile affect the economic burden related to AE. Conclusion This study provided real-world evidence of the economic burden of AEs associated with the use of PD-1 inhibitors in Brazil. This work also made methodological contributions by evaluating the economic burden of AE of PD-1 inhibitors considering the kinetics of toxicity occurrence and categorizing the costs in terms of CMO, CMN and TMC.

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Assessment of the Clinical Trials Safety Profile of PD-1/PD-L1 Inhibitors Among Patients With Cancer: An Updated Systematic Review and Meta-Analysis

Cited by 3 publications

References 74 publications

Risk of Rash in PD-1 or PD-L1-Related Cancer Clinical Trials: A Systematic Review and Meta-Analysis

Risk of Rash in PD-1 or PD-L1-Related Cancer Clinical Trials: A Systematic Review and Meta-Analysis

The role of lncRNAs and circRNAs in the PD-1/PD-L1 pathway in cancer immunotherapy

Does it fit in your pocket? economic burden of PD-1 inhibitors' toxicity in the supplementary health system: evidence from Brazil

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