Neoadjuvant immunotherapy and neoadjuvant chemotherapy in resectable non-small cell lung cancer: A systematic review and single-arm meta-analysis

Abstract

Background: It remains uncertain whether neoadjuvant immune checkpoint inhibitor (nICI) is superior to neoadjuvant chemotherapy (nCT) in resectable non-small cell lung cancer. In addition, there are outstanding questions for nICI such as the ideal treatment mode and predictors.

Methods: PubMed, Embase, Cochrane Library, Web of Science, and scientific meetings were searched for eligible single-arm or multi-arm trials until 31 December 2021. The primary outcomes of interest were major pathological response (MPR) and pathological complete response (pCR). The random-effect model was used for statistical analysis.

Results: Twenty-four trials of nICI (n = 1,043) and 29 trials of nCT (n = 2,337) were identified. nICI combination therapy was associated with higher MPR (63.2%, 95% CI: 54.2%-72.1%) and pCR (35.3%, 95% CI: 27.4%-43.3%) rates compared to nCT (16.2%, 95% CI: 7.5%-25.0%, P < 0.001 and 5.5%, 95% CI: 3.5%-7.5%, P < 0.001) and nICI monotherapy (23.3%, 95% CI: 12.7%-33.8%, P < 0.001, and 6.5%, 95% CI: 1.7%-11.2%, P < 0.001). As for safety, nICI monotherapy had the best tolerability; nICI combination showed a similar surgical resection rate and higher R0 resection rate compared to nCT. PD-1 inhibitor and high PD-L1 expression (≥1% or ≥50%) were correlated with higher MPR and pCR rates compared to PD-L1 inhibitor and PD-L1 expression <1%.

Conclusions: nICI combination therapy is associated with higher MPR and pCR rates compared to nCT and nICI monotherapy. PD-1 inhibitor seems to be superior to PD-L1 inhibitor. PD-L1 status appears to be predictive of MPR and pCR for patients receiving nICI.

Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=278661, CRD42021278661.

Keywords: chemotherapy; immune checkpoint inhibitor; meta-analysis; neoadjuvant; non-small cell lung cancer; pathological response.

Figure 1

Literature search and selection. ICI, checkpoint inhibitor; CT, chemotherapy.

Figure 2

Outcomes of neoadjuvant CT vs. neoadjuvant ICI combination therapy vs. neoadjuvant ICI monotherapy. MPR, major pathologic response; pCR, pathological complete response; ORR, objective response rate; TRAEs, treatment-related adverse events; ICI, checkpoint inhibitor; CT, chemotherapy.

Figure 3

Subgroup analyses for MPR and pCR in patients receiving neoadjuvant ICI. MPR, major pathologic response; pCR, pathological complete response; ICI, checkpoint inhibitor; CT, chemotherapy; RT; radiotherapy; CRT; chemoradiotherapy; SCC, squamous cell carcinoma; NSCC, non-squamous cell carcinoma.