AUTHOR=Qi Yihang , Zhang Wenxiang , Jiang Ray , Xu Olivia , Kong Xiangyi , Zhang Lin , Fang Yi , Wang Jingping , Wang Jing 

TITLE=Efficacy and safety of PD-1 and PD-L1 inhibitors combined with chemotherapy in randomized clinical trials among triple-negative breast cancer

JOURNAL=Frontiers in Pharmacology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.960323

DOI=10.3389/fphar.2022.960323

ISSN=1663-9812

ABSTRACT=<p><bold>Background:</bold> The combination of immune checkpoint inhibitors (ICIs) and chemotherapy (CT) is a new strategy to explore cancer treatment in recent years, and it is also practiced in triple-negative breast cancer (TNBC). However, several published randomized controlled trials (RCTs) reported heterogeneous results. We conducted this meta-analysis to yield insights into the efficacy and safety of the combination of ICIs and CT for TNBC patients in both the adjuvant and neoadjuvant settings.</p><p><bold>Method:</bold> EMBASE, PUBMED, Cochrane, and <ext-link ext-link-type="uri" xlink:href="http://www.clinicaltrials.gov" xmlns:xlink="http://www.w3.org/1999/xlink">www.clinicaltrials.gov</ext-link> databases were searched to determine potential eligible studies from the inception to 20 May 2022. Published RCTs on PD-1/PD-L1 ICIs combined with CT for TNBC patients were included.</p><p><bold>Result:</bold> This meta-analysis included six double-blind RCTs comprising 4,081 TNBC patients treated with PD-1 or PD-L1 ICIs plus CT or placebo plus CT. The combination strategy benefited a better pathologic complete response (pCR) by 29% (RR = 1.29; 95% CI: 1.17–1.41; I<sup>2</sup> = 0%) and a better progression-free survival (PFS) (HR = 0.82; 95% CI: 0.74–0.90; I<sup>2</sup> = 0%) in the neoadjuvant and the adjuvant settings, respectively, especially in PD-L1-positive population (HR = 0.71; 95% CI: 0.62–0.81; I<sup>2</sup> = 13%). The safety profiles were generally tolerable in both settings but the combination treatment will increase the risk of severe adverse events in the adjuvant setting (RR = 1.33; 95% CI 1.08–1.62, I<sup>2</sup> = 0%). Additionally, the combination will increase the risk of any-grade hypothyroidism, hyperthyroidism, pneumonia, and rash in the adjuvant setting, and the risk of any-grade hypothyroidism, hyperthyroidism, infusion-related reactions, and severe cutaneous reactions in the neoadjuvant setting.</p><p><bold>Conclusion:</bold> This meta-analysis demonstrated a significant pCR benefit and confirms the PFS benefit with PD-1/PD-L1 ICIs plus CT in TNBC patients with tolerable safety events in both neoadjuvant and adjuvant settings.</p>