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      Safety and efficacy of atezolizumab in the treatment of cancers: a systematic review and pooled-analysis

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          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Purpose

          Immune checkpoint inhibitors have developed rapidly and have demonstrated antitumor activity in various cancers. To evaluate the safety and efficacy of atezolizumab in treating cancers, we conducted this meta-analysis.

          Methods

          Embase, PubMed, MEDLINE, the Central Register of Controlled Trials of the Cochrane Library, and the American Society of Clinical Oncology database were searched for relevant studies. The primary outcomes were any grade adverse events (AEs) and grade ≥3 AEs. The secondary outcomes were overall objective response rate, pooled 6-month progression-free survival (PFS) rate, 1-year overall survival (OS) rate, median PFS, and median OS.

          Results

          Our meta-analysis was based on 14 clinical trials with 3,266 patients. The total risk of any grade AEs reached 69%, while grade ≥3 AEs happened in only 13% of participants. The overall atezolizumab-related death rate was 0.17%. Major common AEs involved fatigue (24.5%), decreased appetite (13.2%), nausea (12.3%), diarrhea (10.8%), pyrexia (10.7%), pruritus (9.6%), cough (9.5%), edema peripheral (8.6%), and rash (8.4%). The most common severe AEs were fatigue (2.2%), anemia (1.9%), and dyspnea (1.9%). Meanwhile, we found that 6% patients reached complete response and 16% partial response. The pooled 6-month PFS rate and 1-year OS rate were 0.36 (95% CI: 0.31–0.41) and 0.55 (95% CI: 0.49–0.61), respectively. The median PFS varied from 1.5 to 6.1 months, and the median OS ranged from 5.9 to 28.9 months.

          Conclusion

          Atezolizumab has a considerable potential in treating cancers with an acceptable risk profile.

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          Most cited references 16

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          Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade.

           Y Iwai,  M. Ishida,  Y. Tanaka (2002)
          PD-1 is a receptor of the Ig superfamily that negatively regulates T cell antigen receptor signaling by interacting with the specific ligands (PD-L) and is suggested to play a role in the maintenance of self-tolerance. In the present study, we examined possible roles of the PD-1/PD-L system in tumor immunity. Transgenic expression of PD-L1, one of the PD-L, in P815 tumor cells rendered them less susceptible to the specific T cell antigen receptor-mediated lysis by cytotoxic T cells in vitro, and markedly enhanced their tumorigenesis and invasiveness in vivo in the syngeneic hosts as compared with the parental tumor cells that lacked endogenous PD-L. Both effects could be reversed by anti-PD-L1 Ab. Survey of murine tumor lines revealed that all of the myeloma cell lines examined naturally expressed PD-L1. Growth of the myeloma cells in normal syngeneic mice was inhibited significantly albeit transiently by the administration of anti-PD-L1 Ab in vivo and was suppressed completely in the syngeneic PD-1-deficient mice. These results suggest that the expression of PD-L1 can serve as a potent mechanism for potentially immunogenic tumors to escape from host immune responses and that blockade of interaction between PD-1 and PD-L may provide a promising strategy for specific tumor immunotherapy.
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            Molecular pathways: next-generation immunotherapy--inhibiting programmed death-ligand 1 and programmed death-1.

            The aim of T-cell-based immune therapy for cancer has been to generate durable clinical benefit for patients. Following a generation of therapies that largely showed minimal activity, substantial toxicity, and no biomarkers to identify which patients benefit from treatment, early studies are showing signs that programmed death-ligand 1 (PD-L1) and programmed death-1 (PD-1) inhibitors are highly active. Preclinical and early data from clinical studies suggest that targeting this pathway can induce durable clinical responses in patients in a variety of tumor types, including lung and colon cancer. Furthermore, correlations with tumor PD-L1 expression may enable selection of patients most likely to benefit from treatment. The emerging data not only offer the hope of better cancer therapy but also provide evidence that changes our understanding of how the host immune system interacts with human cancer. ©2012 AACR.
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              PD-L1 expression in melanoma shows marked heterogeneity within and between patients: implications for anti-PD-1/PD-L1 clinical trials.

              This study evaluated the expression of PD-L1 in immunotherapy-naïve metastatic melanoma patients to determine longitudinal intrapatient concordance and correlate PD-L1 status with clinicopathologic characteristics and outcome. PD-L1 expression was assessed by immunohistochemistry in 58 patients (43 primary tumors, 96 metastases). Seventy-two percent of patients had at least one specimen expressing PD-L1 in ≥ 1% of tumor cells. Median positive tumor cell count overall was low (8% in nonzero specimens). PD-L1 expression was frequently discordant between primary tumors and metastases and between intrapatient metastases, such that 23/46 longitudinal patient specimens were discordant. PD-L1 was associated with higher TIL grade but not with other known prognostic features. There was a positive univariate association between PD-L1 expression in locoregional metastases and melanoma-specific survival, but the effect was not observed for primary melanoma. In locoregional lymph node metastasis, PD-L1+/TIL+ patients had the best outcome, and PD-L1+/TIL- patients had poor outcome.
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                Author and article information

                Journal
                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                Drug Design, Development and Therapy
                Dove Medical Press
                1177-8881
                2019
                04 February 2019
                : 13
                : 523-538
                Affiliations
                [1 ]Cancer Center, West China Hospital, Sichuan University, Chengdu, China, mingliu721@ 123456aliyun.com
                [2 ]State Key Laboratory of Biotherapy and Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, China, mingliu721@ 123456aliyun.com
                [3 ]Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China
                [4 ]Department of Gynecology, West China Second Hospital, Sichuan University, Chengdu, China
                [5 ]Department of Medical Oncology, First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China
                Author notes
                Correspondence: Ming Liu, Cancer Center, West China Hospital, Sichuan University, 37 Guoxue Alley, Chengdu 610041, China, Tel +86 288 547 5576, Fax +86 288 547 5576, Email mingliu721@ 123456aliyun.com
                Article
                dddt-13-523
                10.2147/DDDT.S188893
                6366347
                © 2019 Tie et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                Categories
                Original Research

                Pharmacology & Pharmaceutical medicine

                meta-analysis, atezolizumab, cancer, efficacy, safety

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