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
. 2023 Dec:195:113404.
doi: 10.1016/j.ejca.2023.113404. Epub 2023 Oct 26.

Systematic review and meta-analysis of immune checkpoint inhibitors as single agent or in combination with chemotherapy in early-stage non-small cell lung cancer: Impact of clinicopathological factors and indirect comparison between treatment strategies

Antonio Nuccio  1 , Giuseppe Viscardi  2 , Fabio Salomone  3 , Alberto Servetto  3 , Francesco Maria Venanzi  4 , Silvia Teresa Riva  5 , Sara Oresti  4 , Francesca Rita Ogliari  4 , Mariagrazia Viganò  4 , Alessandra Bulotta  4 , Robert Cameron  6 , Alessandra Esposito  6 , Jacobi Hines  6 , Roberto Bianco  3 , Michele Reni  1 , Tina Cascone  7 , Marina Chiara Garassino  6 , Valter Torri  8 , Giulia Veronesi  9 , Michela Cinquini  8 , Roberto Ferrara  10
Affiliations
Meta-Analysis

Systematic review and meta-analysis of immune checkpoint inhibitors as single agent or in combination with chemotherapy in early-stage non-small cell lung cancer: Impact of clinicopathological factors and indirect comparison between treatment strategies

Antonio Nuccio et al. Eur J Cancer. 2023 Dec.

Abstract

Background: In non-small cell lung cancer (NSCLC), the immune checkpoint inhibitors (ICI) revolution is rapidly moving from metastatic to early-stage, however, the impact of clinicopathological variables and optimal treatment sequencing remain unclear.

Methods: Randomized controlled trials (RCTs) in patients with early-stage NSCLC treated with ICI as single agent or in combination with platinum-based chemotherapy (PCT) were included. Primary outcomes were pathological complete response (pCR), event free survival (EFS) (neoadjuvant/perioperative), and disease-free survival (DFS) (adjuvant). Secondary outcomes were major pathological response (MPR), overall survival (OS), toxicity, surgical outcomes (neoadjuvant/perioperative); OS and toxicity (adjuvant). An additional secondary endpoint was to compare EFS and OS between neoadjuvant and perioperative strategies.

Results: 8 RCTs (2 neoadjuvant, 4 perioperative, 2 adjuvant) (4661 participants) were included. Neoadjuvant/perioperative ICI+PCT significantly improved pCR, EFS, OS, MPR and R0 resection compared to PCT. Adjuvant ICI significantly improved DFS compared to placebo. There was a significant subgroup interaction by PD-L1 status (χ2 = 10.72, P = 0.005), pCR (χ2 = 17.80, P < 0.0001), and stage (χ2 = 4.46, P = 0.003) for EFS. No difference according to PD-L1 status was found for pCR, with 14% of patients having PD-L1 negative tumors still experiencing a pCR. No interaction by PD-L1 status was found for DFS upon adjuvant ICI. Indirect comparison showed no difference in EFS and OS between neoadjuvant and perioperative ICI+PCT.

Conclusions: PD-L1 status, pCR and stage impact on survival upon neoadjuvant/perioperative ICI. The restriction of neoadjuvant/perioperative ICI to PD-L1 + patients could preclude pCR and long-term benefit in the PD-L1- subgroup. Neoadjuvant and perioperative could be equivalent strategies.

Keywords: Adjuvant; Early-stage; Immune checkpoint inhibitors; Meta-analysis; NSCLC; Neoadjuvant; pCR.

PubMed Disclaimer

Conflict of interest statement

Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: T.C. reports (over the past 36 months) speaker fees/honoraria from the Society for Immunotherapy of Cancer (SITC), Mark Foundation for Cancer Research, Bristol Myers Squibb, Roche, Medscape, IDEOlogy Health, Physicians' Education Resource® LLC (PER®), OncLive, PeerView and Clinical Care Options (CCO); advisory role/consulting fees from MedImmune/AstraZeneca, Bristol Myers Squibb, Merck & Co., Genentech, Arrowhead Pharmaceuticals, Pfizer Inc. and Regeneron; institutional research funding from MedImmune/AstraZeneca and Bristol Myers Squibb; and travel, food and/or beverage expenses from Physicians' Education Resource® LLC (PER®), Dava Oncology, SITC, International Association for the Study of Lung Cancer, Parker Institute for Cancer Immunotherapy, IDEOlogy Health, OncLive, AstraZeneca and Bristol Myers Squibb.M.C.G. reports AstraZeneca, Abion, MSD International GmbH, Bayer, BMS, Boehringer Ingelheim Italia S.p.A, Celgene, Eli Lilly, Incyte, Novartis, Pfizer, Roche, Takeda, Seattle Genetics, Mirati, Daiichi Sankyo, Regeneron, Merck, Blueprint, Jansenn, Sanofi, AbbVie, BeiGenius, Oncohost, Medscape G.V. is consultant for Ab Medica, Roche, AstraZeneca, MSD, outside the submitted work R.F. reports advisory board for MSD and advisory board for BeiGene M.R. declares grants or contracts from AstraZeneca and participation on a Data Safety Monitoring Board or Advisory Board for Eli Lilly, PANAVANCE, Celgene, AstraZeneca, Viatris, Merck Sharp & Dohme, Servier, SOTIO, and Baxter. All remaining authors have declared no conflicts of interest.

Figures

Fig. 1.
Fig. 1.
pCR, MPR and surgical outcomes (R0 resection and not resected patients) (neoadjuvant) (A), 1-year EFS/PFS and OS rates (neoadjuvant) (B), 1-year DFS and OS rates (adjuvant) (C), grade 3–5 treatment related adverse events (neoadjuvant and adjuvant) (D).
Fig. 2.
Fig. 2.
Forest plots for pCR (A), EFS/PFS in neoadjuvant RCTs (B) and for DFS in adjuvant RCTs (C).
Fig. 3.
Fig. 3.
pCR (A), EFS/PFS (B) and DFS (C) according to PD-L1 TPS, EFS/PFS according to pCR.
Fig. 3.
Fig. 3.
pCR (A), EFS/PFS (B) and DFS (C) according to PD-L1 TPS, EFS/PFS according to pCR.
Fig. 3.
Fig. 3.
pCR (A), EFS/PFS (B) and DFS (C) according to PD-L1 TPS, EFS/PFS according to pCR.
Fig. 3.
Fig. 3.
pCR (A), EFS/PFS (B) and DFS (C) according to PD-L1 TPS, EFS/PFS according to pCR.
Fig. 4.
Fig. 4.
Comparison of EFS/PFS (A) and OS (B) between perioperative and neoadjuvant strategies.
See this image and copyright information in PMC

References

    1. Mountzios G, Remon J, Hendriks LEL, García-Campelo R, Rolfo C, Van Schil P, et al. Immune-checkpoint inhibition for resectable non-small-cell lung cancer — opportunities and challenges. Nat Rev Clin Oncol 2023;20:664–77. 10.1038/s41571-023-00794-7. - DOI - PubMed
    1. Rainey MA, Allen CT, Craveiro M. Egress of resident memory T cells from tissue with neoadjuvant immunotherapy: Implications for systemic anti-tumor immunity. Oral Oncol 2023;146:106570. 10.1016/j.oraloncology.2023.106570. - DOI - PMC - PubMed
    1. Topalian SL, Forde PM, Emens LA, Yarchoan M, Smith KN, Pardoll DM. Neoadjuvant immune checkpoint blockade: a window of opportunity to advance cancer immunotherapy. Cancer Cell 2023;41:1551–66. 10.1016/j.ccell.2023.07.011. - DOI - PMC - PubMed
    1. Besse B, Adam J, Cozic N, Chaput-Gras N, Planchard D, Mezquita L, et al. 1215O - SC Neoadjuvant atezolizumab (A) for resectable non-small cell lung cancer (NSCLC): results from the phase II PRINCEPS trial. Ann Oncol 2020;31:S794–5. 10.1016/j.annonc.2020.08.1417. - DOI
    1. Shu CA, Gainor JF, Awad MM, Chiuzan C, Grigg CM, Pabani A, et al. Neoadjuvant atezolizumab and chemotherapy in patients with resectable non-small-cell lung cancer: an open-label, multicentre, single-arm, phase 2 trial. Lancet Oncol 2020;21:786–95. 10.1016/S1470-2045(20)30140-6. - DOI - PubMed

MeSH terms