Abstract 194P
Background
In the early stages, the use of neoadjuvant treatment is the standard of care in triple negative breast cancers (TNBCs). Patients who achieve a pathological complete response (pCR) with primary therapy have improved survival outcomes. The programmed cell death protein 1 (PD-1) is an immune checkpoint that inhibits T-cell effector function within tissues. Its ligand, PD-L1, has been shown to have high expression in TNBCs. To date, major research efforts are being undertaken to determine the use of PD-1/PD-L1 immune checkpoint inhibitors in TNBC. Recent randomized controlled trials (RCTs) have shown promising activity of PD-1/PD-L1 inhibitors in the neo-adjuvant setting.
Methods
A systematic search of Pubmed, Embase, Cochrane, Clinical trials databases and hand search were utilized to identify RCTs investigating the use of neoadjuvant PD-1/PD-L1 inhibitors plus standard chemotherapy in TNBC. Trials published up to March 2020 were included. Using the random effects model, pooled Odds ratios (ORs) with 95% confidence intervals (CI) were calculated for pCR. Subgroup analysis of pCR rates based on PD-L1 expression was also done.
Results
Four RCTs were included (N=384) and analyzed. Neoadjuvant immunotherapy plus chemotherapy showed significant pCR benefit of 58.5% vs 42.2% compared to chemotherapy alone (OR1.76, 95%CI1.11-2.79,P<0.02). Subgroup analysis based on PD-L1 expression showed that in the immunotherapy group, there is a significantly higher pCR rate in the PD-L1-positive population than in the PD-L1 negative group (64.5%vs39.4%, OR1.55, 95%CI 1.16-2.09, p=0.003, I2 = 0%). Adverse events were generally consistent with known safety profiles.
Conclusions
PD-1/PD-L1 inhibitors combined with chemotherapy was associated with increased pCR rates in TNBC, hence, supporting its use in the neo-adjuvant setting. Subgroup analysis showed that the benefit of adding immunotherapy was more significant in those with PD-L1-expressing tumors. This indicates that the PD-L1 immune marker may have utility in selecting TNBC patients who can benefit more from PD-L1 inhibitors. Longer follow-up of these studies would hopefully show significance in progression-free survival and overall survival.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.