Immune checkpoint inhibitors as neoadjuvant therapy in early triple-negative breast cancer: A systematic review and meta-analysis

Context: Immune checkpoint inhibitors combined with chemotherapy are being evaluated in neoadjuvant settings in early triple-negative breast cancer (TNBC). Aim: To evaluate efficacy and safety of checkpoint inhibitors in early TNBC. Methods: Electronic search was done using PubMed, EMBASE, Google Scholar, Cochrane Central Register of Controlled Trials and clinicaltrials.gov to identify relevant articles till October 31, 2020. Clinical trials evaluating checkpoint inhibitors as neoadjuvant therapy in early-stage TNBC were included. Outcomes assessed included pathologic complete response (pCR), event-free survival (EFS), and safety. Statistical Analysis Used: Meta-analysis was conducted using Cochrane review manager (RevMan) version 5.4. Randomized controlled trials (RCTs) were assessed for quality using Cochrane Collaboration risk of the bias assessment tool, version 2.0 (ROB-2). GRADE analysis was done to assess the overall quality of evidence for all outcomes. Results: Out of 116 studies screened, 5 RCTs were included in meta-analysis. Compared to control group, programmed death-1 (PD-1)/programmed death-ligand 1 (PDL-1) inhibitor group was associated with significant increase in rate of pCR (odd ratio [OR] =1.71 [1.38–2.11]; P < 0.00001) and EFS (1.77 [1.21–2.60]; P = 0.003). There was a significant increase in risk of serious adverse events (risk ratio [RR] =1.53 [1.28-1.83]; P < 0.00001), adverse events of special interest (AESI) of any grade (RR: 1.5 [1.34–1.69], P < 0.00001) and grade 3 or higher AESI (RR: 2.8 [1.87–4.19], P < 0.00001) with PD-1/PDL-1 inhibitors compared to control. Conclusions: PD-1/PDL-1 inhibitors in combination with neoadjuvant chemotherapy for early TNBC show significant improvement in pCR irrespective of PDL-1 status and cancer stage.