Response Efficacy of PD-1 and PD-L1 Inhibitors in Clinical Trials: A Systematic Review and Meta-Analysis

Chen, Shixue; Zhang, Zhibo; Zheng, Xuan; Tao, Haitao; Zhang, Sujie; Ma, Junxun; Liu, Zhefeng; Wang, Jinliang; Qian, Yongmei; Cui, Pengfei; Huang, Di; Huang, Ziwei; Wu, Zhaozhen; Hu, Yi

doi:10.3389/fonc.2021.562315

Cited by 61 publications

(55 citation statements)

References 109 publications

(29 reference statements)

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“…In our study, seven patients developed PD after only two cycles of immunotherapy-based therapy, which may be due to the early resistance to the combined agents rather than ICI. Previous studies showed a delayed onset of action of ICIs with a median time to response of 2.05–3.3 months (Chen et al 2021 ; Hida et al 2017 ; Rizvi et al 2015 ). After re-administration of ICI and change of the combined regimens, these patients responded well.…”

Section: Discussionmentioning

confidence: 96%

Immune checkpoint inhibitor rechallenge in advanced or metastatic non-small cell lung cancer: a retrospective cohort study

Hao

Yang

et al. 2022

J Cancer Res Clin Oncol

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Purpose After progression to immunotherapy, the standard of care for non-small cell lung cancer (NSCLC) was limited. Administration of the same or different immune checkpoint inhibitors (i.e., ICI rechallenge) may serve as a novel option. The present study aimed to evaluate the efficacy of ICI rechallenge for NSCLC and explore prognostic factors. Methods In this retrospective cohort study, data of advanced or metastatic NSCLC patients rechallenged with ICI at the Cancer Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College between December 2018 and June 2021 were retrieved. Progression-free, overall survivals (PFS; OS), etc. were calculated. Subgroup analyses were conducted according to baseline characteristics, prior treatment results, etc. for prognostic factor exploration using the Cox model. Results Forty patients were included. Median age was 59 years. Thirty-one (78%) were male. Twenty-seven (68%) were smokers. Adenocarcinoma (28 [70%]) was the major histological subtype. Median PFS of patients receiving initial ICI was 5.7 months. The most common rechallenge regimens were ICI plus chemotherapy and/or angiogenesis inhibitor (93%). Seventeen (43%) were rechallenged with another ICI. Median PFS for ICI rechallenge was 6.8 months (95% CI 5.8–7.8). OS was immature. Tendencies for longer PFS were observed in nonsmoker or patients with adenocarcinoma, response of stable/progressive disease in initial immunotherapy, or whose treatment lines prior to ICI rechallenge were one/two. However, all results of prognostic factors were nonsignificant. Conclusion ICI rechallenge may be an option for NSCLC after progress to immunotherapy. Further studies to confirm the efficacy and investigate prognostic factors are warranted.

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Section: Discussionmentioning

confidence: 96%

Immune checkpoint inhibitor rechallenge in advanced or metastatic non-small cell lung cancer: a retrospective cohort study

Hao

Yang

et al. 2022

J Cancer Res Clin Oncol

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“…Compared to PD-1 inhibitors, PD-L1 inhibitors are usually not associated with significant conformational changes in PD-L1 [13]. Moreover, such discrepancies might be related to the substantial variations in the mechanisms of action of a single PD-1/PD-L1 blockade agent [15,38]. Based on discrepancies in the mechanisms of action between PD-1/PD-L1 inhibitors, more attention is being paid to the differences between anti-PD-1 and anti-PD-L1 treatments in clinical practice, and evidence-based analysis to understand their comparable efficacies is urgently required [15].…”

Section: Discussionmentioning

confidence: 99%

Comparative Impact of PD-1 and PD-L1 Inhibitors on Advanced Esophageal or Gastric/Gastroesophageal Junction Cancer Treatment: A Systematic Review and Meta-Analysis

Kim

Lee

2021

JCM

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Programmed death 1 (PD-1) and PD ligand 1 (PD-L1) inhibitors have demonstrated varying effectiveness in treating esophageal or gastric/gastroesophageal junction (G/GEJ) cancer. Hence, this systematic review and meta-analysis evaluated the efficacy and safety of anti-PD-1/PD-L1 treatment in patients with esophageal or G/GEJ cancer by analyzing the types of medications. Randomized controlled trials comparing anti-PD-1/PD-L1 to control therapy were identified by searching PubMed, EMBASE, and ClinicalTrials.gov. The outcomes included overall survival (OS), progression-free survival (PFS) rates, and serious adverse events (SAEs), evaluating the differences in therapy types, including a comparison between PD-1 and PD-L1 inhibitors. Eight studies were included in the analysis. PD-1/PD-L1 inhibitors affected the overall OS rate increment without influencing the PFS rate (HR, 0.837; 95% CI, 0.753–0.929; p = 0.001; HR 0.991; 95% CI, 0.778–1.263; p = 0.942, respectively). Anti-PD-1 was significantly more beneficial for increasing OS and PFS than PD-L1 inhibitors. Anti-PD-1 and PD-L1 use was not significantly associated with SAE development in esophageal or G/GEJ cancer patients. PD-1/PD-L1 inhibitor use was associated with improved OS and PFS rate increase among PD-1 and PD-L1 inhibitors. Considering response variations to anti-PD-1/PD-L1 usage, more individualized treatments should be introduced in clinical practice.

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“…So far, Food and Drug Administration (FDA) has approved six monoclonal antibodies targeting PD1 (nivolumab, pembrolizumab, and cemiplimab) or PDL1 (atezolizumab, Durvalumab and avelumab) for the treatment of hematological and solid malignancies. ( Tan et al, 2016 ; Chen et al, 2021 ). Monoclonal antibodies (mAb), known as checkpoint inhibitors, overcome the shortcomings of traditional anticancer therapies and inhibit the PD1/PDL1 mutual effect.…”

Section: Mechanism Of Action and Treatment Of Pd1/pdl1 Inhibitorsmentioning

confidence: 99%

“…The anti-CTLA-4 antibody ipilimumab has shown durable anti-tumor activity and prolonged survival in patients with advanced melanoma, but is prone to immune-related adverse events (IAEs) ( Buchbinder et al, 2016 ). PD1/PDL1 inhibitors are promising immunotherapeutic agents that can achieve satisfactory efficacy for different tumor types, different treatment routes, different drug combinations and different treatment regimens ( Chen et al, 2021 ). The incidence of PD1/PDL1 inhibitor-mediated IAEs was significantly lower compared to CTLA-4 blockade ( Ott et al, 2013 ).…”

Section: Introductionmentioning

confidence: 99%

PD-1/PD-L1 Checkpoint Inhibitors in Tumor Immunotherapy

et al. 2021

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Programmed death protein 1 (PD1) is a common immunosuppressive member on the surface of T cells and plays an imperative part in downregulating the immune system and advancing self-tolerance. Its ligand programmed cell death ligand 1 (PDL1) is overexpressed on the surface of malignant tumor cells, where it binds to PD1, inhibits the proliferation of PD1-positive cells, and participates in the immune evasion of tumors leading to treatment failure. The PD1/PDL1-based pathway is of great value in immunotherapy of cancer and has become an important immune checkpoint in recent years, so understanding the mechanism of PD1/PDL1 action is of great significance for combined immunotherapy and patient prognosis. The inhibitors of PD1/PDL1 have shown clinical efficacy in many tumors, for example, blockade of PD1 or PDL1 with specific antibodies enhances T cell responses and mediates antitumor activity. However, some patients are prone to develop drug resistance, resulting in poor treatment outcomes, which is rooted in the insensitivity of patients to targeted inhibitors. In this paper, we reviewed the mechanism and application of PD1/PDL1 checkpoint inhibitors in tumor immunotherapy. We hope that in the future, promising combination therapy regimens can be developed to allow immunotherapeutic tools to play an important role in tumor treatment. We also discuss the safety issues of immunotherapy and further reflect on the effectiveness of the treatment and the side effects it brings.

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Response Efficacy of PD-1 and PD-L1 Inhibitors in Clinical Trials: A Systematic Review and Meta-Analysis

Cited by 61 publications

References 109 publications

Immune checkpoint inhibitor rechallenge in advanced or metastatic non-small cell lung cancer: a retrospective cohort study

Immune checkpoint inhibitor rechallenge in advanced or metastatic non-small cell lung cancer: a retrospective cohort study

Comparative Impact of PD-1 and PD-L1 Inhibitors on Advanced Esophageal or Gastric/Gastroesophageal Junction Cancer Treatment: A Systematic Review and Meta-Analysis

PD-1/PD-L1 Checkpoint Inhibitors in Tumor Immunotherapy

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