Immune Checkpoint Inhibitors Combined With Chemotherapy Compared With Chemotherapy Alone for Triple-Negative Breast Cancer: A Systematic Review and Meta-Analysis

Abstract

BackgroundIt is still controversial whether immune checkpoint inhibitors (ICIs) can improve the curative effect when added to original standard chemotherapy treatment for triple-negative breast cancer (TNBC). We compared their antitumor efficacy and adverse effects (AEs) to make a better clinical decision.MethodsSeven databases were searched for eligible articles. Progression-free survival (PFS), overall survival (OS), and AEs were measured as the primary outcomes.ResultsNine randomized controlled trials (RCTs) involving 4,501 patients were included. ICI+chemotherapy treatment achieved better PFS (hazard ratio [HR]: 0.78, [0.70–0.86], p < 0.00001), OS (HR: 0.86, [0.74–0.99], p = 0.04), and complete response (584/1,106 vs. 341/825, risk ratio [RR]: 1.38, [1.01–1.89], p = 0.04). With the prolongation of survival, the survival advantage of ICI+chemotherapy increased compared with chemotherapy. Subgroup analysis suggested that the addition of ICIs might not have a better effect in Asian patients, patients with locally advanced disease, or patients with brain metastases. In the toxicity analysis, more Grade 3–5 AEs and serious AEs were found in the ICI+chemotherapy group. For Grade 3–5 AEs, more cases of diarrhea, severe skin reactions, pneumonitis, hepatitis, and adrenal insufficiency were related to the ICI+chemotherapy group.ConclusionsICI+chemotherapy appears to be better than chemotherapy alone for TNBC treatment, with better OS and PFS. However, its high rates of serious AEs need to be taken seriously.Systematic Review RegistrationPROSPERO Registration: CRD42021276394.

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

“…reported that any-grade dermatitis/rash was related to the shortest median Yunhai Li et, al. and Ji Qiao et, al. conducted metaanalyses regarding the efficacy and safety of the combination of ICIs and chemotherapy among TNBC patients (Ji et al, 2021;Li et al, 2021), which reported similar results as ours. Additionally, the differences lie mainly in the following aspects: 1) our study included and analyzed both neoadjuvant and adjuvant studies, while Yunhai Li et, al.…”

“…merely focused on the adjuvant setting and Ji Qiao et, al. only paid attention to the adjuvant setting; 2) we analyzed and discussed the discrepancies of adverse events in detail between these two settings to sort out the adverse events that require additional attention due to the different combined strategies of ICIs; 3) subgroup analyses of OS in adjuvant setting according to age, race, baseline disease status, metastatic sites, neoadjuvant therapy, previous treatment, and so on were well-performed by Ji Qiao et, al, through which they reported that the Asian patients, patients with locally advanced disease, and patients with brain metastases might not benefit from the addition of ICIs (Ji et al, 2021).…”

Dysregulation of systemic soluble immune checkpoints in early breast cancer is attenuated following administration of neoadjuvant chemotherapy and is associated with recovery of CD27, CD28, CD40, CD80, ICOS and GITR and substantially increased levels of PD-L1, LAG-3 and TIM-3

“…The first of these, which encompassed six randomized controlled trials focused on early TNBC (n=2142 patients), reported that NAC in combination with PD-1/PD-L1 inhibitors also resulted in improved pCR rates and event-free survival ( 29 ). The second included eight randomized controlled trials, encompassing 4901 patients with both early and metastatic TNBC (four trials in each category) ( 30 ). The authors of this study reported improved OS and PFS in patients treated with immunotherapy together with chemotherapy relative to those treated with chemotherapy alone ( 30 ).…”

Immunotherapy in triple-negative breast cancer: Insights into tumor immune landscape and therapeutic opportunities

“…However, the largest benefit of checkpoint inhibitor therapy arises from its combination with chemotherapy. This combination is hypothesized to increase tumor cell death by adding a second mechanism of action to standard cytotoxic agents and by taking advantage of the immune modulating effects of standard therapies (Denkert et al, 2018;Luen et al, 2019;Ji et al, 2021). Combination of atezolizumab with either paclitaxel (Miles et al, 2021) or carboplatin and nab-paclitaxel (ASCO, 2020) did not result in improvements in efficacy or safety outcomes relative to chemotherapy alone.…”