Clinical efficacy and safety of anti-PD-1/PD-L1 treatments in non-small cell lung cancer (NSCLC)

Zeng, Tian; Qin, Qin; Zhi-heng, Bian; Li, Jianjun

doi:10.1080/21691401.2019.1687499

Cited by 11 publications

(7 citation statements)

References 42 publications

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“…In many advanced-stage cancer types, such as unresectable or metastatic melanoma [58,59], non-small cell lung cancer (NSCLC) [60], advanced renal cell carcinoma [61], metastatic squamous head & neck [62], and relapsed or refractory Hodgkin lymphoma [63] ICI is an approved anti-cancer treatment and yields high rates of tumor regression [64]. Also, in contrast to chemotherapy, ICI is administered in a single dose once in 2-6 weeks based on the medication and cancer type.…”

Section: Expert Opinionmentioning

confidence: 99%

Immune checkpoint inhibition in COVID-19: risks and benefits

Pezeshki

Rezaei

2021

Expert Opinion on Biological Therapy

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Introduction Immune checkpoint inhibition (ICI) is a novel cancer immunotherapy, which is administered in patients with metastatic, refractory, or relapsed solid cancer types. Since the initiation of the Coronavirus Disease 2019 (COVID-19) pandemic, many studies have reported a higher severity and mortality rate of COVID-19 among patients with cancer in general. Areas covered The immunomodulatory effects of ICI can modify the patients’ immune system function in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. There is controversy over whether the severity of COVID-19 in cancer patients who previously received ICI compared to other patients with cancer has increased. There is evidence that the upregulation of immune checkpoint molecules in T cells, lymphopenia, and inflammatory cytokine secretion are associated with the severity of COVID-19 symptoms. Expert opinion ICI can interrupt the T cell exhaustion and depletion by interrupting the inhibitory signaling of checkpoint molecules in T cells, and augments the immune system response in COVID-19 patients with lymphopenia. However, ICI may also increase the risk of cytokine release syndrome. ICI can be considered not only as a cancer immunotherapy but also as immunotherapy in COVID-19. More studies are needed to assess the safety of ICI in COVID-19 patients with or without cancer.

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Section: Expert Opinionmentioning

confidence: 99%

Immune checkpoint inhibition in COVID-19: risks and benefits

Pezeshki

Rezaei

2021

Expert Opinion on Biological Therapy

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“…The interruption of PD-1 engagement by its ligand reinvigorates the immune system, allowing immune-mediated anti-cancer responses to resume, leading to marked clinical responses in some cancers ( 9 ). Anti-PD-1 and anti-PD-L1 antibodies such as nivolumab, pembrolizumab, cemiplimab, and atezolizumab, durvalumab, avelumab have shown promising results in several cancer types ( 10 , 11 ). Nivolumab and pembrolizumab have been approved as first-line agents in recurrent/metastatic HNSCC patients by the United States Food and Drug Administration (FDA) ( 7 , 12 ).…”

Section: Introductionmentioning

confidence: 99%

Programmed Death-1/Programmed Death-Ligand 1-Axis Blockade in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma Stratified by Human Papillomavirus Status: A Systematic Review and Meta-Analysis

Zhu

Maroun

et al. 2021

Front. Immunol.

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BackgroundProgrammed death-1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors have provided clinical benefit to head and neck squamous cell carcinoma (HNSCC) patients in recent clinical trials. However, it remains unclear as to whether human papillomavirus (HPV) status is associated with improved clinical outcome of anti-PD-1 or anti-PD-L1 immunotherapy in HNSCC.MethodsPubMed, EMBASE, Cochrane Library, and Web of Science were systematically searched up to February 28, 2021. Published clinical trials of HNSCC patients treated with only PD-1 or PD-L1 inhibitors were selected. The primary or secondary outcome of these studies included objective response rate (ORR) stratified by HPV status. The pooled odds ratio (OR) and hazard ratio (HR) were estimated using a fixed-effect model.ResultsA total of seven eligible studies comprising 814 patients were included. The ORR of HPV positive HNSCC patients was significantly higher than that of HPV negative HNSCC patients (OR = 1.77; 95%CI = 1.14-2.74; P = 0.01), and this favorable effect occurred in pooled anti-PD-L1 trials (OR = 2.66; 95%CI = 1.16-6.11; P = 0.02). In comparison, the pooled OR was 1.51 in anti-PD-1 trials (95%CI = 0.90-2.54; P = 0.12). Survival analysis indicated that HPV positive HNSCC patients had a lower risk of overall death as compared to HPV negative HNSCC patients (HR = 0.77; 95%CI = 0.60–0.99; P = 0.04).ConclusionsHPV positive HNSCC patients display improved outcomes with PD-1/PD-L1 axis blockade as compared to HPV negative HNSCC patients. These improved outcomes are likely driven to a greater extent by anti-PD-L1 inhibitors. However, randomized controlled trials with greater numbers of patients are needed for validation of these early findings.

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“…Results of Zeng et al. ( 54 ) indicated that the OS rate was prolonged by anti-PD-1/PD-L1, as well as PFS. Meanwhile, the authors also demonstrated that anti-PD-1/PD-L1 could greatly enhance the objective response rate (ORR) with fewer adverse events.…”

Section: Discussionmentioning

confidence: 99%

“…But there are no trials simultaneously investigating the efficacy and safety of all five therapeutic options (avelumab, atezolizumab, cemiplimab, nivolumab, and pembrolizumab). To date, two traditional meta-analyses were conducted to explore the efficacy of anti-PD-1/PD-L1 treatments (includes nivolumab, pembrolizumab, and atezolizumab) vs. chemotherapy in patients with NSCLCs ( 54 , 55 ). And one NMA only assessed the difference in both efficacy and safety profiles among nivolumab, pembrolizumab, and atezolizumab in pretreated NSCLC patients ( 56 ).…”

Section: Discussionmentioning

confidence: 99%

Comparative Efficacy and Safety of Anti-PD-1/PD-L1 for the Treatment of Non-Small Cell Lung Cancer: A Network Meta-Analysis of 13 Randomized Controlled Studies

et al. 2022

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ObjectiveThe present network meta-analysis (NMA) was conducted to summarize the direct and indirect evidence of common programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors including avelumab, atezolizumab, cemiplimab, nivolumab, and pembrolizumab for the treatment of non-small cell lung cancer (NSCLC) patients and further to determine the optimal therapeutic regimen.MethodsWe performed a systematic literature search to identify all potentially eligible studies in PubMed, Embase, and the Cochrane Library until August 7, 2021. The primary outcome was overall survival (OS), and the second outcome was treatment-related adverse events (TRAEs). We used random-effects model to conduct direct and network meta-analyses, which were performed by using RevMan 5.3 and R version 3.6.1, respectively.ResultsDirect meta-analysis suggested that atezolizumab, cemiplimab, nivolumab, or pembrolizumab significantly improved OS compared with chemotherapy (CT), and NMA further established that atezolizumab [hazard ratio (HR), 0.77; 95% CrI, 0.62–0.96], nivolumab (HR, 0.75; 95% CrI, 0.62–0.93), or pembrolizumab (HR, 0.71; 95% Credible interval (Crl), 0.57–0.89) significantly and cemiplimab (HR, 0.68; 95% CrI, 0.46–1.02) numerically improved OS compared with CT. Meanwhile, NMA also indicated that cemiplimab was numerically superior to other PD-1/PD-L1 agents. Moreover, avelumab, atezolizumab, cemiplimab, nivolumab, and pembrolizumab were found to have fewer TRAEs compared with CT in direct meta-analysis, which were supported by the results from the NMA. Meanwhile, surface under the cumulative ranking curve (SUCRA) and ranking probability suggested that cemiplimab provided the most favorable balance between efficacy and safety, with the first ranking for the OS.ConclusionsBased on available evidence, cemiplimab may have the most favorable risk–benefit ratio for NSCLC patients compared with other common therapeutic management. However, future research with a large-scale, high-quality, and mature follow-up is needed to further determine which agents should be preferentially selected for NSCLC patients due to the limitations of our NMA and variations of eligible studies in treatment line and PD-L1 status.

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Clinical efficacy and safety of anti-PD-1/PD-L1 treatments in non-small cell lung cancer (NSCLC)

Cited by 11 publications

References 42 publications

Immune checkpoint inhibition in COVID-19: risks and benefits

Immune checkpoint inhibition in COVID-19: risks and benefits

Programmed Death-1/Programmed Death-Ligand 1-Axis Blockade in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma Stratified by Human Papillomavirus Status: A Systematic Review and Meta-Analysis

Comparative Efficacy and Safety of Anti-PD-1/PD-L1 for the Treatment of Non-Small Cell Lung Cancer: A Network Meta-Analysis of 13 Randomized Controlled Studies

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