The efficacy and safety of anti-PD-1/PD-L1 antibodies for treatment of advanced or refractory cancers: a meta-analysis

Zhang, Tengfei; Xie, Jing; Arai, Seiji; Wang, Liping; Shi, Xiaoguang; Shi, Ning; Ma, Fen; Chen, Sen; Huang, Lan; Li, Yang; Ma, Wei; Zhang, Bin; Han, Weidong; Xia, Jianchuan; Hu, Chen; Zhang, Yi

doi:10.18632/oncotarget.12230

Cited by 78 publications

(67 citation statements)

References 48 publications

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“…Meta‐analyses of the safety and tolerability of anti–PD‐L1/PD‐1 agents corroborate findings of improved safety profiles of ICIs compared with chemotherapy regimens used to treat patients with advanced cancers 28, 29, 30, 31. 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.…”

Section: Discussionmentioning

confidence: 60%

“…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. Treatment with ICIs was associated with a higher incidence of any‐grade and grade 3 to 4 irAEs (ie, rash, aspartate aminotransferase increase, hypothyroidism, colitis, and pneumonitis) compared with non‐ICI regimens 31.…”

Section: Discussionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 60%

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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“…We consider that nivolumab treatment prior to osimertinib treatment should be considered with caution when devising a treatment strategy for patients with EGFR-mutated advanced NSCLC. The presence of PD-L1 expression has been reported to be a predictive biomarker of the efficacy of anti-PD-1/PD-L1 antibodies, including nivolumab (13). Assessment of tumor PD-L1 expression may aid with decision-making regarding the adoption of nivolumab treatment in patients with EGFR-mutated advanced NSCLC.…”

Section: Discussionmentioning

confidence: 99%

Osimertinib-induced interstitial lung disease in a patient with non-small cell lung cancer pretreated with nivolumab: A case report

Takakuwa

Oguri

Uemura

et al. 2017

Molecular and Clinical Oncology

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Abstract. Osimertinib (AZD9291) is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor approved for EGFR-T790M-positive non-small cell lung cancer. A high incidence of interstitial lung disease (ILD) during combination treatment with osimertinib and anti-programmed cell death-ligand 1 (PD-L1) inhibitor has been reported. The current study presents a case of ILD development during osimertinib treatment following nivolumab (an anti-PD-1 antibody) treatment. The 59-year-old female was diagnosed with stage IV lung adenocarcinoma harboring a deletion in exon 19 of the EGFR gene. Following nivolumab as a sixth-line treatment, an EGFR-T790M-encoding mutation in EGFR exon 20 was identified by re-biopsy. Osimertinib was therefore initiated as a seventh-line treatment. A partial response was subsequently noted; however, 63 days after initiation of the treatment the patient presented with dyspnea with decreased oxygenation in the absence of fever and sputum. A computed tomography scan revealed the emergence of ground-glass opacities with bronchiectasis in both lungs, and a diagnosis of ILD due to osimertinib was made. Following steroid pulse therapy with discontinuation of osimertinib, the patient's chest findings and respiratory condition improved. Therefore, it is considered that anti-PD-1 therapies may be associated with a risk of ILD during subsequent osimertinib treatment. IntroductionThe discovery of epidermal growth factor receptor (EGFR)-acti vating mutations in non-small cell lung cancer (NSCLC) and EGFR tyrosine kinase inhibitors (TKIs) have changed the strategy of NSCLC therapy. Recently, EGFR-TKIs, including gefitinib, erlotinib and afatinib, have become the standard therapy for patients with advanced EGFR-mutated NSCLC. However, the majority of the patients progress and second-line therapy is required.The EGFR T790M point mutation (T790M) is the most common mechanism underlying drug resistance to EGFR-TKIs in EGFR mutation-positive NSCLC patients. Osimertinib (AZD9291) is a third-generation EGFR-TKI approved for the treatment of EGFR-T790M-positive NSCLC (1). Furthermore, immune checkpoint modulation with programmed death-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibition has also shown promise in changing the strategy of NSCLC therapy. Nivolumab, an anti-PD-1 inhibitor, is a novel drug used in the second-line treatment of NSCLC (2). In both EGFR-TKI and immune checkpoint inhibitors therapy, interstitial lung disease (ILD) is recognized as one of most severe adverse events. These two therapies may be sequentially applied in the same patient, but the effects of the interaction between these two drugs on the risk of ILD remains unclear. A case of ILD that occurred during osimertinib treatment in a patient with a history of previous nivolumab treatment is reported herein. Case reportA 59-year-old female was diagnosed with stage IV (cT3N2M1a) lung adenocarcinoma harboring a deletion in exon 19 of the EGFR gene. The patient was treated with platinum-pemetrexed with bevacizumab...

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“…In patients with melanoma, monoclonal antibodies against PD-1 have shown to be more effective when compared with ipilimumab and chemotherapy 12. Ipilimumab, ipilimumab followed by pembrolizumab/nivolumab sequence or usage of pembrolizumab/nivolumab directly has been described in the literature.…”

Section: Introductionmentioning

confidence: 99%

Immune checkpoint inhibitors in the management of malignancies in transplant recipients

Regalla

Williams

Paluri

2018

Postgraduate Medical Journal

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Cancer immunotherapy, an area of active research, has thus far yielded several exciting breakthroughs in cancer treatment strategies. So far, immune checkpoint inhibitors have been the most promising method of cancer immunotherapy. CTLA-4, PD-1 and PD-L1 are the immune checkpoint molecules against which monoclonal antibodies act against and revolutionised the treatment of several malignancies. However, it is still unclear whether using these monoclonal antibodies in patients with malignancy and a history of transplant is as beneficial as in patients without a history of transplantation. The reason being, with the therapeutic benefit, also comes the inherent disadvantage of transplant rejection because of the activation of T-cells against donor antigens. So, transplant-related complications limit the usage of the checkpoint blockade therapy to treat malignancies. Here, we review the data published in this context and suggest optimal approaches to using the currently available repertoire of immunotherapies.

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The efficacy and safety of anti-PD-1/PD-L1 antibodies for treatment of advanced or refractory cancers: a meta-analysis

Cited by 78 publications

References 48 publications

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

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

Osimertinib-induced interstitial lung disease in a patient with non-small cell lung cancer pretreated with nivolumab: A case report

Immune checkpoint inhibitors in the management of malignancies in transplant recipients

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