The efficacy of neoadjuvant immune checkpoint inhibitors in lung squamous cell carcinoma and adenocarcinoma: a systematic review and single-arm meta-analysis

Background: Neoadjuvant immunotherapy is effective in treating resectable non-small cell lung cancer (NSCLC) but shows different responses in lung squamous cell carcinoma (SCC) and adenocarcinoma (ADC). Current studies are limited in size, necessitating further research to clarify these differences. This study aims to investigate whether there is a difference between the efficacy of neoadjuvant immune checkpoint inhibitors (ICIs) on lung SCC vs. ADC.

Methods: Studies provided data of pathological or radiological response of ADC and SCC receiving neoadjuvant ICIs published before August 1, 2023, were retrieved. Pathological response included major pathological response (MPR), complete pathological response (cPR) and the sum of major pathological response and complete pathological response (McPR). Radiological response includes complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), objective response rate (ORR), disease control rate (DCR). The protocol was registered in the Prospective Register of Systematic Reviews (PROSPERO CRD42022328240).

Results: A total of 22 studies with 430 patients were included. Pathological response and radiological response were used to evaluate the efficacy of neoadjuvant immunotherapy on ADC and SCC. No significant difference was found in pathological response (MPR: P=0.15; cPR: P=0.61), while SCC had significantly higher ORR (P=0.02), lower SD (P<0.04) and PD (P=0.04) than ADC after neoadjuvant ICIs. Both SCC and ADC achieved significantly higher PR (P<0.01), ORR (P<0.01), and lower SD (P<0.01) when treated with chemo-immunotherapy compared to ICI monotherapy. Chemo-immunotherapy significantly improved the McPR in ADC (P<0.05). Toripalimab showed a higher ORR for both SCC and ADC (P<0.05) without a clear advantage in pathological remission across the ICIs. Pembrolizumab had significantly higher McPR (P<0.05) for treating SCC patients compare to ADC patients.

Conclusions: In conclusion, our findings indicate that SCC patients exhibited higher ORR and lower SD and PD than those with ADC. No significant differences in pathological responses were seen between SCC and ADC, across ICI monotherapy or chemo-immunotherapy. Chemo-immunotherapy notably improved McPR in ADC. Toripalimab showed higher ORR in both cancers without distinct pathological remission advantage. Pembrolizumab, however, demonstrated superior McPR in SCC, indicating a preference in treating SCC.