In the early stages, the use of neo-adjuvant systemic treatment is the standard of care in TNBCs. Patients who achieve a pathological complete response (pCR) have improved survival outcomes. The programmed cell death receptor ligand, PD-L1, has been shown to have high expression in TNBCs. To date, major research efforts are being undertaken to determine the applicability of PD-1/PD-L1 immune checkpoint inhibitors in TNBC.
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 that were published up to March 2020 were included and were appraised. 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.
Four RCTs were included (N=384). The addition of immunotherapy to chemotherapy in the neo-adjuvant setting showed significant pCR benefit of 58.5% vs 42.2% compared to chemotherapy alone (OR 1.76, 95% CI 1.11-2.79, P <0.02). Subgroup analysis based on PD-L1 expression showed that in the immunotherapy plus chemotherapy group, there is a significantly higher pCR rate in the PD-L1-positive population than in the PD-L1 negative group (64.5% vs 39.4%). The addition of immunotherapy showed a significant benefit in improving pCR in the PD-L1-positive group (OR 1.55, 95%CI 1.16-2.09, p = 0.003, I2 =0%).
The addition of PD-1/PD-L1 inhibitors to standard chemotherapy is associated with increased pCR rates in patients with TNBC, hence, supporting its use for patients 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 result 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 and further analysis of these studies would hopefully demonstrate significance in other outcomes such as progression-free survival and overall survival.
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All authors have declared no conflicts of interest.