10P - Neoadjuvant immunotherapy plus chemotherapy in early triple-negative breast cancer: A meta-analysis of randomized controlled trials

Background

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.

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 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.

Results

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%).

Conclusions

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.

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.