Programmed cell death/programmed cell death ligand 1 (PD-1/PD-L1) inhibitors have preliminarily shown encouraging results as neoadjuvant setting. No data reported on randomized trials comparing neoadjuvant immunotherapy and chemotherapy leaving undetermined critical issues for better clinical treatment options.
We conducted a systemic review of trials involving neoadjuvant immunotherapy and chemotherapy, performing an indirect comparison meta-analysis of neoadjuvant immunotherapy and neoadjuvant chemotherapy upon multiple short-term outcome.
This systematic review and meta-analysis included 10 trials of neoadjuvant immunotherapy and 11 neoadjuvant chemotherapy involving 1755 patients. Patients received PD-1/PD-L1 inhibitors alone (13.3%; 95%CI, 9.0%-19.3%) had lower objective response rate (ORR) compared to PD-1/PD-L1 inhibitors plus chemotherapy (62.5%; 95%CI, 54.4%-70.0%) or chemotherapy (41.6%; 95%CI, 36.8%-46.7%) while neoadjuvant PD-1/PD-L1 inhibitors plus chemotherapy (36.2%; 95%CI, 19.2%-57.6%) achieved elevated complete pathological complete response (pCR) eclipsing PD-1/PD-L1 inhibitors alone (10.6%; 95%CI, 6.5%-16.9%) and standard chemotherapy (7.5%; 95%CI, 5.7%-9.8%). Neoadjuvant chemotherapy (87.2%; 95%CI, 74.9%-94.0%) has numerically lower R0 resection rate in contrast to neoadjuvant PD-1/PD-L1 inhibitors alone (92.7%; 95%CI, 83.4%-97.0%) and PD-1/PD-L1 inhibitors plus chemotherapy (91.6%; 95%CI, 84.3%-95.7%). Subgroup analysis showed that increased proportion of stage III patients receiving neoadjuvant chemotherapy (p=0.025, Spearman r=0.761) may be correlated with lower R0 resection rate while no significant correlation was found in PD-1/PD-L1-based neoadjuvant treatment.
Compared to neoadjuvant chemotherapy, immunotherapy-based regimens provided superior pathological response along with higher complete resection rate especially for stage III disease. Immunotherapy combined chemotherapy as neoadjuvant setting may be a more preferable clinical option currently.
Wen-zhao Zhong.
National Natural Science Foundation.
All authors have declared no conflicts of interest.