Efficacy and safety of neoadjuvant immunotherapy in non-small cell lung cancer: a systematic review and meta-analysis

Background: Several studies have been conducted to confirm the efficacy and safety of neoadjuvant immunotherapy. However, the effects and safety of different types of immune checkpoint inhibitors (ICIs) and drug combinations are still uncertain due to the limited results published. Furthermore, a discussion of possible biomarkers needs to be put on the agenda. Consequently, an analysis of the latest research is urgently needed. Methods: PubMed, OVID, Cochrane Library, and international conferences up to October 1, 2021, were searched. Radiologic outcomes [objective response rate (ORR)], pathologic outcomes [major pathological response (MPR), pathological complete response (pCR)], surgical outcomes [surgical resection rate, R0 surgical resection rate (R0 rate), the incidence of surgical complications, surgical delay rate], and adverse events [treatment -related adverse event (TRAE), 3-5 grade TRAE] were extracted. Possible biomarkers in connection with pathologic response were also explored. Results: Our study contained 19 trials, with 859 patients included. The efficacy of neoadjuvant immunotherapy was higher than neoadjuvant chemotherapy published earlier. In subgroup analysis, the combined strategy (immunotherapy plus chemotherapy) exhibited better performance. Compared with immunotherapy alone, combined treatment performed better in ORR (64.8% vs. 11.9%), MPR (64.1% vs. 23.6%), and pCR (35.4% vs. 5.2%) though with more adverse events. Programmed cell death protein 1 (PD1) inhibitor was associated with fairly higher effectiveness (ORR: 43.1% vs. 32.0%) and lower incidence of 3-5 grade TRAE [14.1%; 95% confidence interval (CI), 5.1-26.6%] compared with programmed cell death protein ligand 1 (PD -L1) inhibitor (27.0%; 95% CI, 0-89.8%). The rate of MPR in the PD -L1 positive group was significantly higher [relative risk (RR) =1.56; 95% CI, 1.06-2.29]. High -expression group also performed well (RR =3.38; 95% CI, 1.20-9.52). When we compared the group with objective response and the group without objective response, RR reached 3.19 (95% CI, 2.17-4.69), indicating ORR was probably in connection with MPR as well. We found no significant results in other factors such as smoking status, histological type, gender, and clinical stage. Similar results were found in patients with pCR. Conclusions: Our study further confirmed that neoadjuvant immunotherapy combined with chemotherapy had preferable efficacy and acceptable safety. Based on combined therapy, applying PD -1 inhibitor were preferred in clinical practice. Furthermore, our study proved that PD -L1 expression level may be the possible biomarker in connection with the pathologic response of either MPR or pCR.