Table 2.

Summary of Phase 3 clinical trials of immune checkpoint inhibition for triple negative breast cancer in the neoadjuvant and metastatic settings

	Early-stage TNBC Neoadjuvant clinical trials	Metastatic TNBC Metastatic clinical trials
Assay used for PD-L1 expression detection	KEYNOTE 522 [113] : 22C3 IMpassion 031[115]: SP142	KEYNOTE 355 [127] : 22C3 IMpassion 130[123], IMpassion 131[125]: SP142
Scored area	KEYNOTE 522: TC, lymphocytes, and macrophages IMpassion 031: tumor-infiltrating IC	KEYNOTE 355: TC, lymphocytes, and macrophages IMpassion 130, IMpassion 131: tumor-infiltrating IC
Definition of PD-L1 positivity	KEYNOTE 522: CPS = PD-L1 + cells (TC+IC)/TC*100 ≥ 1 IMpassion 031: PD-L1 + IC/tumor area (IC%) ≥ 1%	KEYNOTE 355: CPS ≥ 1, CPS ≥ 10 IMpassion 130, IMpassion 131: IC% ≥ 1%
Experimental immune checkpoint antibody	KEYNOTE 522: Pembrolizumab IMpassion 031: Atezolizumab	KEYNOTE 355: Pembrolizumab IMpassion 130, IMpassion 131: Atezolizumab
Chemotherapy backbone	KEYNOTE 522: PCb-EC/AC IMpassion 031: nab-paclitaxel-AC	KEYNOTE 355: nab-paclitaxel; paclitaxel; or GCb IMpassion 130: nab-paclitaxel IMpassion 131: paclitaxel
Premedication with corticosteroids	KEYNOTE 522: Yes IMpassion 031: No	KEYNOTE 355: Yes in the paclitaxel arm IMpassion 130: No IMpassion 131: Yes
Primary endpoint (Experimental group vs. Control group)	KEYNOTE 522: pCR (ypT0/Tis ypN0) ITT population: 64.8% vs. 51.2%, rate difference 13.6 (95%CI: 5.4-21.8), P < 0.001 PD-L1 + subgroup: 68.9% vs. 54.9%, rate difference 14.2 (95%CI: 5.3-23.1) IMpassion 031: pCR (ypT0/Tis ypN0) ITT population: 58% vs. 41% rate difference 17 (95%CI: 6-27), one-sided P = 0.0044 (significance boundary 0·0184) PD-L1 + subgroup: 69% vs. 49%, rate difference 20 (95%CI: 4-35), interactive P = 0.52	KEYNOTE 355: PFS ITT population: 7.5 months vs. 5.6 months, HR = 0.82 (95%CI: 0.69-0.97), P value not available CPS ≥ 10 subgroup: 9.7 months vs. 5.6 months, HR = 0.65 (95%CI: 0.49-0.86), P = 0.0012 (significance boundary 0.00411) CPS ≥ 1 subgroup: 7.6 months vs. 5.6 months, HR = 0.74, (95%CI: 0.61-0.90), P = 0.0014 (significance boundary 0.00111) IMpassion 130: PFS ITT population: 7.2 months vs. 5.5 months, HR = 0.80 (95%CI: 0.69-0.92), P = 0.002 PD-L1 + subgroup: 7.5 months vs. 5.0 months, HR = 0.64 (95%CI: 0.51-0.80), P < 0.001 IMpassion 131: PFS ITT population: 5.7 months vs. 5.6 months, HR = 0.86 (95%CI: 0.70-1.05), P value not available PD-L1 + subgroup: 6.0 months vs. 5.7 months, HR = 0.82 (95%CI: 0.60-1.12), P = 0.20
Primary clinical outcome dependent upon PD-L1 expression	KEYNOTE 522: No IMpassion 031: No	KEYNOTE 355: CPS ≥ 1, No; CPS ≥ 10, Yes IMpassion 130: Yes IMpassion 131: No

TNBC: Triple negative breast cancer; TC: tumor cells; IC: immune cells; CPS: combined positive score; PCb: paclitaxel plus carboplatin; AC: doxorubicin plus cyclophosphamide; EC: epirubicin plus cyclophosphamide; GCb: gemcitabine plus carboplatin; pCR: pathological complete response; CI: confidence intervals; PFS: progression-free survival; ITT: intention-to-treat; HR: hazard ratio; PD-L1: programmed death-ligand 1.