Safety and Tolerability of PD-1/PD-L1 Inhibitors Compared with Chemotherapy in Patients with Advanced Cancer: A Meta-Analysis

Nishijima, Tomohiro F.; Shachar, Shlomit Strulov; Nyrop, Kirsten A.; Muss, Hyman B.

doi:10.1634/theoncologist.2016-0419

Cited by 247 publications

(182 citation statements)

References 35 publications

(47 reference statements)

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“…27 In this review, we investigated the quality of AE reporting as a surrogate of the reliability of AE rates reported in RCTs manuscripts. 27 In this review, we investigated the quality of AE reporting as a surrogate of the reliability of AE rates reported in RCTs manuscripts.…”

Section: Discussionmentioning

confidence: 99%

A systematic review of adverse events in randomized trials assessing immune checkpoint inhibitors

Arnaud-Coffin

Maillet

Gan

et al. 2019

Intl Journal of Cancer

191

163

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The advent of immune checkpoint‐inhibitors (CPI) has transformed treatment for several cancer types. This review was performed to assess the rate of adverse events (AEs) associated with the use of CPI, alone or in combinations. A review of AEs reporting quality was also performed. All publications of Randomized Clinical Trials (RCTs) assessing CPI published before December 2017 were included. To investigate the quality of AEs reporting, a set of items was defined based on the 2004 CONSORT harms extension statement. Rates of Grade 5, serious, and study‐withdrawal related AEs were collected in each treatment category. Specific immune related AEs (irAEs) were also collected when available. Pooled estimates of adverse event rates were calculated by using generalized linear mixed model. A total of 35 RCTs including 16,485 patients were included. The overall quality of AEs reporting was satisfactory, but items pertaining to methods of data collection and analysis were infrequently reported. Grade ≥ 3 AEs were reported for 14% (95% CI 12–16) of patients treated with PD(L)‐1 inhibitors, 34% (95% CI 27–42) of patients treated with CTLA‐4 inhibitors, 55% (95% CI 51–59) of patients on CPI combinations and 46% (95% CI 40–53) of patients on immunotherapy‐chemotherapy combination. The profile of irAEs was different among the treatment categories. The use of CPI, especially in combination, is associated with significant rates of Grade ≥ 3 AEs. Healthcare planning should anticipate the expected high number of patients presenting with irAEs in the future.

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Section: Discussionmentioning

confidence: 99%

A systematic review of adverse events in randomized trials assessing immune checkpoint inhibitors

Arnaud-Coffin

Maillet

Gan

et al. 2019

Intl Journal of Cancer

191

163

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“…In a meta‐analysis of 3450 patients from 7 randomized controlled trials, treatment with ICIs was associated with a lower incidence of any‐grade AEs compared with chemotherapy (67.6% vs 82.9%) and grade 3 to 4 AEs (11.4% vs 35.7%), and treatment discontinuation occurred less frequently with anti–PD‐L1/PD‐1 agents compared with chemotherapy (4.5% vs 11.1%) 28. The incidence of TRAEs associated with ICIs ranged from 9% to 31%, with a pooled rate of 16% (95% confidence interval, 12%‐21%) 30.…”

Section: Discussionmentioning

confidence: 99%

Safety profile of avelumab in patients with advanced solid tumors: A pooled analysis of data from the phase 1 JAVELIN solid tumor and phase 2 JAVELIN Merkel 200 clinical trials

Kelly

Infante

Taylor

et al. 2018

Cancer

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BACKGROUNDAntibodies targeting the programmed death‐ligand 1 (PD‐L1)/programmed cell death protein 1 (PD‐1) checkpoint may cause adverse events (AEs) that are linked to the mechanism of action of this therapeutic class and unique from those observed with conventional chemotherapy.METHODSPatients with advanced solid tumors who were enrolled in the phase 1 JAVELIN Solid Tumor (1650 patients) and phase 2 JAVELIN Merkel 200 (88 patients) trials received avelumab, a human anti–PD‐L1 IgG1 antibody at a dose of 10 mg/kg every 2 weeks. Treatment‐related AEs (TRAEs) were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.0). In post hoc analyses, immune‐related AEs (irAEs) were identified via an expanded AE list and medical review, and infusion‐related reactions (IRRs) occurring ≤2 days after infusion and symptoms occurring ≤1 day after infusion and resolving ≤2 days after onset were identified based on prespecified Medical Dictionary for Regulatory Activities (MedDRA) terms.RESULTSOf the 1738 patients analyzed, grade ≥3 TRAEs occurred in 177 (10.2%); the most common were fatigue (17 patients; 1.0%) and IRR (10 patients; 0.6%). TRAEs led to discontinuation in 107 patients (6.2%) and death in 4 patients (0.2%). Grade ≥3 irAEs occurred in 39 patients (2.2%) and led to discontinuation in 34 patients (2.0%). IRRs or related symptoms occurred in 439 patients (25.3%; grade 3 in 0.5% [9 patients] and grade 4 in 0.2% [3 patients]). An IRR occurred at the time of first infusion in 79.5% of 439 patients who had an IRR, within the first 4 doses in 98.6% of 439 patients who had an IRR, and led to discontinuation in 35 patients (2.0%).CONCLUSIONSAvelumab generally was found to be well tolerated and to have a manageable safety profile. A minority of patients experienced grade ≥3 TRAEs or irAEs, and discontinuation was uncommon. IRRs occurred mainly at the time of first infusion, and repeated events were infrequent. Cancer 2018;124:2010‐7. © 2018 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

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“…It has been observed that PD1/PD-L1 inhibitors are overall better tolerated than chemotherapy. [27] In lung cancer adenocarcinoma PD-L1 + cases convergence and cavitation were more frequently than did PD-L1 -cases. In contrast, surrounding ground glass opacities and air bronchogram were observed less frequently in PD-L1 + cases than in PD-L1 -cases.…”

Section: Pd-l1mentioning

confidence: 94%

First and Best Treatments for EGFR and PD-L1 - Competition for First Line Therapy in Adenocarcinoma

Man¹,

Hohenforst-Schmidt²,

Yarmus³

et al. 2017

Oncomedicine

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Lung cancer is still diagnosed at advanced stages since there are no blood markers or efficient prevention programs. Moreover, lack of early disease symptoms do lead patients for early diagnosis. In the past ten years novel targeted and non-targeted therapies have entered the market for advanced stage disease patients. Epidermal growth factor receptor and anaplastic lymphoma kinase agents are considered an excellent choice as first line treatment for adenocarcinoma. However; in the past few months PD-L1 >50% patients can be treated with immunotherapy as first line treatment. Moreover; second generation tyrosine kinase inhibitors are already on the market in the case of disease relapse in EGFR and ALK positive patients. In the current mini review we will focus on current up-to-date data regarding the best choice between tkis and immunotherapy as first line treatment for adenocarcinoma.

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Safety and Tolerability of PD-1/PD-L1 Inhibitors Compared with Chemotherapy in Patients with Advanced Cancer: A Meta-Analysis

Cited by 247 publications

References 35 publications

A systematic review of adverse events in randomized trials assessing immune checkpoint inhibitors

A systematic review of adverse events in randomized trials assessing immune checkpoint inhibitors

Safety profile of avelumab in patients with advanced solid tumors: A pooled analysis of data from the phase 1 JAVELIN solid tumor and phase 2 JAVELIN Merkel 200 clinical trials

First and Best Treatments for EGFR and PD-L1 - Competition for First Line Therapy in Adenocarcinoma

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