Efficacy and safety of immune checkpoint inhibitors in non-small cell lung cancer

Wang, Shuai; Hao, Jiatao; Wang, Hao; Fang, Yong; Tan, Lijie

doi:10.1080/2162402x.2018.1457600

Cited by 23 publications

(26 citation statements)

References 45 publications

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“…Moreover, their data were obtained from indirect comparisons, and they only included EGFR-TKIs as control therapy. Wang et al 7 demonstrated that ICIs are effective in patients with NSCLC, but this meta-analysis failed to compare different tumour subtypes and focused on anti-PD-1/PD-L1 and anti-CTLA-4 inhibitors concurrently.Here, we performed a systematic review and meta-analysis to compare the clinical efficacy and immune-related AEs of anti-PD-1/PD-L1 inhibitors to optimise the management of advanced or metastatic cancer. Furthermore, we also focused on the association between anti-PD-1/PD-L1 inhibitors and potential subgroup differences, such as ICI monotherapy or ICI-based combined therapy, multiple types of regimens combined with anti-PD-1/PD-L1 inhibitors, and potential biomarkers of immune checkpoint blockade therapy.…”

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confidence: 99%

Clinical efficacy and safety of anti-PD-1/PD-L1 inhibitors for the treatment of advanced or metastatic cancer: a systematic review and meta-analysis

Sun

Zhang

et al. 2020

Sci Rep

147

112

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Anti-PD-1/PD-L1 inhibitors provide a survival advantage over conventional therapies for treatment of advanced or metastatic cancer. However, the factors determining which patients benefit the most from anti-PD-1/PD-L1 inhibitors are unknown, making treatment-related decisions difficult. We performed a systematic review and meta-analysis of acquired data to assess the efficacy and toxicity of anti-PD-1/ PD-L1 inhibitors in advanced and metastatic cancer. A thorough search strategy was applied to identify randomised controlled trials (RCTs) in Pubmed, Embase, Cochrane, and major conferences. Studies meeting predefined selection criteria were selected, and two independent investigators performed data extraction; overall survival (OS), progression-free survival (PFS), and overall response rate were compared between anti-PD-1/PD-L1 inhibitors and control therapies. We calculated the pooled response rate and 95% CIs of all-grade and high-grade (≥3) adverse effects and evaluated the withinstudy heterogeneity using subgroup, sensitivity, and meta-regression analyses. In final, we included eligible 35 RCTs (21047 patients). The main estimated hazard ratios (HRs) for OS and PFS were 0.76 (0.71-0.82) and 0.81 (0.73-0.89) in a random-effects model. The anti-PD-1/PD-L1 inhibitor group had a significantly high risk for all-grade immune-related adverse events. Anti-PD-1/PD-L1 inhibitors were identified as a preferable treatment option for advanced or metastatic cancer patients who are male, aged < 65 years, current or former smokers, had no CNS or liver metastasis, had not EGFR mutation, and had high PD-L1 expression.Cancer is a common cause of death, accounting for more than 9.56 million deaths annually 1 . Over half of cancer patients have a poor prognosis due to locally advanced or systemic metastasis. For the majority of these cases, treatment with conventional therapies, such as chemotherapy and radiotherapy, does not improve their prognosis. Recently, several immune checkpoint inhibitors (ICIs), have been developed and approved for a wide range of tumour types and having shown potential for maintaining homeostasis and eliminating tumour cells. Immunotherapies targeting immune checkpoint pathways have shown potential for generating a durable response and for prolonging disease stabilisation in a significant proportion of inoperable, advanced, or recurrent cancers in patients with multiple cancer types, along with favourable tolerability. In addition to their use as a monotherapy, the general safety of immune checkpoint agents also allows for their use in the development of combined therapies for cancer treatment; combining ICIs with other conventional treatments or targeted therapies is expected to improve anti-tumour activity and increase ICI efficacy. However, although durable responses were reported in cancer patients treated with combination strategies involving ICIs, it is still necessary to optimise dose selection to minimise the adverse events (AEs) caused by combination regimens while maintaining stable clinical ef...

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confidence: 99%

Clinical efficacy and safety of anti-PD-1/PD-L1 inhibitors for the treatment of advanced or metastatic cancer: a systematic review and meta-analysis

Sun

Zhang

et al. 2020

Sci Rep

147

112

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“…One possible explanation is that their mechanisms are different. CTLA‐4 is mainly expressed on T lymphocytes and PD‐1/ PD‐L1 is pervasively expressed on B cells, T cells, myeloid cells, and non‐lymphoid organs . The CTLA‐4 inhibitors can reactivate suppressed T lymphocytes and trigger anti‐tumor response.…”

Section: Discussionmentioning

confidence: 99%

“…CTLA-4 is mainly expressed on T lymphocytes and PD-1/ PD-L1 is pervasively expressed on B cells, T cells, myeloid cells, and non-lymphoid organs. 36,37 The CTLA-4 inhibitors can reactivate suppressed T lymphocytes and trigger anti-tumor response. PD-1/ PD-L1 inhibitors can lead to peripheral T-cell proliferation and infiltration into the tumor, inducing an objective anti-tumor response.…”

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confidence: 99%

Effect of sex on the efficacy of patients receiving immune checkpoint inhibitors in advanced non‐small cell lung cancer

et al. 2019

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Immune checkpoint inhibitors (ICIs) have shown promising efficacy in the treatment of non‐small cell lung cancer (NSCLC). Sex‐associated dimorphism in immune system response is acknowledged, but the effect of patients’ sex on efficacy of ICIs as treatment in NSCLC still remains controversial. The present study was conducted to investigate the difference in efficacy of NSCLC patients receiving immune checkpoint inhibitors according to the sex. A total of 9583 patients involved 6567 men and 3016 women with advanced lung cancer from 15 randomized controlled trials were included in this study. An overall survival (OS) benefit of immune checkpoint inhibitors was illustrated in both male (HR 0.76, 95% CI 0.71‐0.82) and female (HR 0.73, 95% CI 0.58‐0.91) patients, and a progression‐free survival (PFS) benefit was also found in both men (HR 0.67, 95% CI 0.58‐0.77) and women (HR 0.73, 95% CI 0.56‐0.95) in NSCLC. Both PD‐1/PD‐L1 inhibitors alone and PD‐1/PD‐L1 plus chemotherapy significantly improved the OS and PFS in male patients. Whereas in females, PD‐1 inhibitors or monotherapy significantly benefited the OS but not the PFS, PD‐L1 inhibitors or combination therapy significantly prolonged the PFS but not the OS. No survival benefit was found in both male and female patients from the CTLA‐4 inhibitors. The current study indicated that the magnitude of survival benefit is sex‐dependent and male patients seemed to obtain more consistent and favorable outcomes from ICIs than women patients in NSCLC.

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“…Several prospective studies have demonstrated that both ICIs monotherapy and combination regimens showed encouraging efficacies in the treatment of NSCLC . An early meta‐analysis conducted by Wang et al provided clinical evidence that either ICI monotherapy or in combination with chemotherapy improved survival in patients with advanced NSCLC, and ICI group had fewer adverse events (AEs) . However, the meta‐analysis included all lines of treatment, and was not focused on the first‐line treatment.…”

Section: Introductionmentioning

confidence: 99%

“…11,12 An early meta-analysis conducted by Wang et al provided clinical evidence that either ICI monotherapy or in combination with chemotherapy improved survival in patients with advanced NSCLC, and ICI group had fewer adverse events (AEs). 13 However, the meta-analysis included all lines of treatment, and was not focused on the first-line treatment. In addition, several recent randomized controlled trials (RCTs) have reported the latest results and showed more evidence of immunotherapy for the first-line treatment of NSCLC.…”

Section: Introductionmentioning

confidence: 99%

Rational application of the first‐line chemotherapy and immune checkpoint inhibitors in advanced nonsmall cell lung cancer: A meta‐analysis

Cao

Zhang

et al. 2019

Cancer Medicine

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Objective To compare the relative efficacy of immune checkpoint inhibitors (ICIs) or chemotherapy (CT) alone, or their combination modality in the first‐line treatment of advanced nonsmall cell lung cancer (NSCLC). Methods This meta‐analysis was performed on the eligible randomized controlled trials (RCTs) after searching web databases and meeting abstracts. The main research endpoints were the comparisons of median overall survival (mOS), the OS rate of 6 months (OSR6m), 1 year (OSR1y) and 2 years (OSR2y), median progression‐free survival (mPFS), the PFS rate of 6 months (PFSR6m) and 1‐year (PFSR1y), objective response rates (ORR), and treatment‐related adverse events (TRAEs). Results Eleven RCTs comprising 6278 cases were included. In the subgroup of programmed death‐ligand 1 (PD‐L1) ≥50%, compared with chemotherapy, the ICIs showed similar OSR6m ( P > 0.05), but significantly improved efficacy in mOS, OSR1y, OSR2y, and ORR (all P < 0.05), also had less grade ≥ 3 TRAEs. Compared with pembrolizumab alone, pembrolizumab plus CT in the subgroup of PD‐L1 ≥ 50% had similar mOS, OSR6m, OSR1y, and PFSR1y (all P > 0.05), but significantly improved mPFS, PFSR6m, and ORR (all P < 0.05 for interaction). Compared with the CT group, ICIs plus CT group with PD‐L1 ≥ 50% or <1% showed significant benefit in OS, PFS, and ORR (all P < 0.05). However, in the ICIs plus CT group with 1% ≤ PD‐L1 ≤ 49%, only PFS and ORR showed significant benefit compared with CT group (all P < 0.05), but not for results of OS. Conclusions The findings support the rationale for using pembrolizumab alone in the first‐line treatment of PD‐L1 ≥ 50% advanced NSCLC due to the similar OS and lower grade ≥ 3 TRAEs. However, the combination of ICIs and chemotherapy is strongly recommended in patients with PD‐L1 ≤ 49% for significant survival benefit.

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Efficacy and safety of immune checkpoint inhibitors in non-small cell lung cancer

Cited by 23 publications

References 45 publications

Clinical efficacy and safety of anti-PD-1/PD-L1 inhibitors for the treatment of advanced or metastatic cancer: a systematic review and meta-analysis

Clinical efficacy and safety of anti-PD-1/PD-L1 inhibitors for the treatment of advanced or metastatic cancer: a systematic review and meta-analysis

Effect of sex on the efficacy of patients receiving immune checkpoint inhibitors in advanced non‐small cell lung cancer

Rational application of the first‐line chemotherapy and immune checkpoint inhibitors in advanced nonsmall cell lung cancer: A meta‐analysis

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