Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2020 May;235(5):4913-4927.
doi: 10.1002/jcp.29371. Epub 2019 Nov 6.

The landscape of immune checkpoint inhibitor plus chemotherapy versus immunotherapy for advanced non-small-cell lung cancer: A systematic review and meta-analysis

Chengdi Wang  1 , Wenliang Qiao  2 , Yuting Jiang  3 , Min Zhu  1 , Jun Shao  1 , Tao Wang  1 , Dan Liu  1 , Weimin Li  1
Affiliations
Meta-Analysis

The landscape of immune checkpoint inhibitor plus chemotherapy versus immunotherapy for advanced non-small-cell lung cancer: A systematic review and meta-analysis

Chengdi Wang et al. J Cell Physiol. 2020 May.

Abstract

Background: Lung cancer is the leading cause of cancer-related deaths worldwide and the prognosis remains poor. The recent introduction of the immune checkpoint inhibitor (ICI), or plus chemotherapy, both resulted in the survival benefit for patients with advanced non-small-cell lung cancer (NSCLC), but it remains unanswered which is superior. The current study aimed to estimate the comparative efficacy and safety of ICI-chemotherapy versus ICI-monotherapy in advanced NSCLC.

Methods: Studies were identified by searching PubMed, Embase, and Cochrane library. The randomized controlled trials (RCTs) that ICI monotherapy or ICI plus chemotherapy compared with chemotherapy in NSCLC were included with available primary endpoints of progression-free survival (PFS), overall survival (OS), objective response rate, or treatment-related adverse events. A fixed-effect or random-effects model was adopted depending on between-study heterogeneity.

Results: A total of 20 RCTs involving 12,025 patients with NSCLC were included. Both ICI-monotherapy and ICI-chemotherapy resulted in significantly prolonged survival compared to chemotherapy and the former led to significantly longer PFS. The magnitude of survival benefits appeared to be greatest among those treated with pembrolizumab plus platinum-based chemotherapy (OS, 0.56; PFS, 0.54). Additionally, OS and PFS advantages of ICI therapies were observed in patients with NSCLC with low or high programmed cell death 1 ligand 1 (PD-L1) expression level, but not in intermediate PD-L1 TPS.

Conclusions: Pembrolizumab plus platinum-based chemotherapy was recommended as the optimal first-line therapy for advanced patients with NSCLC. Additionally, PD-L1 alone is not recommended as an adequate molecular biomarker to identify eligible patients for routine clinical practice in immunotherapy.

Keywords: chemotherapy; efficacy; immune checkpoint inhibitor; non-small-cell lung cancer; safety.

PubMed Disclaimer

Conflict of interest statement

The authors declare that there are no conflict of interests.

Figures

Figure 1
Figure 1
Forest plots of HRs comparing overall survival between ICI‐chemotherapy and ICI monotherapy. CI, confidence interval; HR hazard ratio; ICI, immune checkpoint inhibitor
Figure 2
Figure 2
Forest plots of HRs comparing progression‐free survival between ICI‐chemotherapy and ICI‐monotherapy. CI, confidence interval; HR hazard ratio; ICI, immune checkpoint inhibitor
Figure 3
Figure 3
Forest plots of RRs comparing objective response rate between ICI‐chemotherapy and ICI‐monotherapy. CI, confidence interval; ICI, immune checkpoint inhibitor; RR, risk ratio
Figure 4
Figure 4
Forest plots of HRs comparing overall survival between ICI therapies and chemotherapy according to PD‐L1 status. CI, confidence interval; HR hazard ratio; ICI, immune checkpoint inhibitor; PD‐L1, programmed cell death 1 ligand 1
Figure 5
Figure 5
Forest plots of RRs comparing Grade 1–5 TRAE between ICI‐chemotherapy and ICI‐monotherapy. CI, confidence interval; ICI, immune checkpoint inhibitor; RR, risk ratio; TRAE, treatment‐related adverse event
Figure 6
Figure 6
Forest plots of RRs comparing Grade 3–5 TRAEs between ICI‐chemotherapy and ICI‐monotherapy. ICI, immune checkpoint inhibitor; RR, risk ratio; TRAE, treatment‐related adverse event
See this image and copyright information in PMC

References

    1. Anagnostou, V. , Smith, K. N. , Forde, P. M. , Niknafs, N. , Bhattacharya, R. , White, J. , … Velculescu, V. E. (2017). Evolution of neoantigen landscape during immune checkpoint blockade in non‐small cell lung cancer. Cancer Discovery, 7(3), 264–276. 10.1158/2159-8290.Cd-16-0828 - DOI - PMC - PubMed
    1. Barlesi, F. , Vansteenkiste, J. , Spigel, D. , Ishii, H. , Garassino, M. , de Marinis, F. , … Park, K. (2018). Avelumab versus docetaxel in patients with platinum‐treated advanced non‐small‐cell lung cancer (javelin lung 200): An open‐label, randomised, phase 3 study. The Lancet Oncology, 19(11), 1468–1479. 10.1016/S1470-2045(18)30673-9 - DOI - PubMed
    1. Borghaei, H. , Paz‐Ares, L. , Horn, L. , Spigel, D. R. , Steins, M. , Ready, N. E. , … Brahmer, J. R. (2015). Nivolumab versus docetaxel in advanced nonsquamous non‐small‐cell lung cancer. The New England Journal of Medicine, 373(17), 1627–1639. 10.1056/NEJMoa1507643 - DOI - PMC - PubMed
    1. Borghaei, H. , David Hellmann, M. , Paz‐Ares, G. , Ramalingam, L., S. , Reck, M S. , John O'Byrne, K. , … Brahmer, J. (2018). Nivolumab (Nivo) + platinum‐doublet chemotherapy (Chemo) vs chemo as first‐line (1L) treatment (Tx) for advanced non‐small cell lung cancer (NSCLC) with <1% tumor PD‐L1 expression: Results from CheckMate 227. Journal of Clinical Oncology, 2018;36:9001.
    1. Brahmer, J. , Reckamp, K. L. , Baas, P. , Crinò, L. , Eberhardt, W. E. E. , Poddubskaya, E. , … Spigel, D. R. (2015). Nivolumab versus docetaxel in advanced squamous‐cell non‐small‐cell lung cancer. The New England Journal of Medicine, 373(2), 123–135. 10.1056/NEJMoa1504627 - DOI - PMC - PubMed

Publication types

MeSH terms