TABLE 1.

Characteristics of clinical trials included for meta-analysis.

Study	NCT number	Title	Status	Conditions	Interventions	Characteristics					Population			Follow-up time frame	CTC for AE version	RECIST version
						Study type	Phase	Study design	Outcome measures	PD-L1 expression assessment	Enrollment	Age	Sex
Emens, 2018	NCT01375842	A study of atezolizumab (an engineered anti-programmed death-ligand 1 [PDL-1] antibody) to evaluate safety, tolerability, and pharmacokinetics in participants with locally advanced or metastatic solid tumors	Completed	• Breast (advanced TNBC) • Tumors • Hematologic malignancies	• Biological: atezolizumab (15 or 20 mg/kg, or at a 1200-mg flat dose, every 3 weeks)	Interventional	Phase 1	• Allocation: randomized • Intervention model: parallel assignment • Masking: none (open label) • Primary purpose: treatment	• Number of participants with dose-limiting toxicities (DLTs) • Maximum tolerated dose (MTD) of atezolizumab • Recommended phase 2 dose (RP2D) of atezolizumab • Percentage of participants with adverse events •Percentage of participants with Anti-therapeutic antibodies (ATAs) • Area under the concentration–time curve (AUC) of atezolizumab etc.	Using the Ventana SP142 immunohistochemistry assay (Ventana Medical Systems), baseline of PD-L1 expression on ICs was evaluated with 4 scoring bins IC3 (≥10%), IC2 (5–10%), IC1 (≥1%,) and IC0 (<1%). The PD-L1 expression on tumor cells (TCs) was assessed as less than 1% (TC0) or at least 1% (TC1/2/3)	661 (115 breast cancer patients)	18 years and older (adult, older adult)	All	Up to 84 months	4	1.1
Adams, 2018	NCT02447003	Study of pembrolizumab (MK-3475) monotherapy for metastatic triple-negative breast cancer (MK-3475–086/KEYNOTE-086)	Active, not recruiting	Breast cancer (advanced TNBC)	• Biological: pembrolizumab (200 mg every 3 weeks)	Interventional	Phase 2	• Intervention model: single group assignment• Masking: none (open label) • Primary purpose: treatment	• Overall response rate (ORR) • Number of participants experiencing at least one adverse event (AE)• Number of participants discontinuing study drug due to AEs • Duration of response (DOR) • Disease control rate (DCR) • Progression-free survival (PFS) • Overall survival (OS) etc.	PD-L1 expression was assessed during screening using the PD-L1 IHC 22C3 pharmDx kit (Agilent, Carpinteria, CA, United States of America). The measure of expression was the combined positive score (CPS), defined as the ratio of PD-l1–positive cells (tumor cells, lymphocytes, and macrophages) out of the total number of tumor cells *100. PD-L1 positivity was defined as CPS ≥1 (previously reported as and equivalent to CPS ≥1%)	285 (all are breast cancer patients)	18 years and older (adult, older adult)	All	Up to 24–27 months	4	1.1
Rugo, 2018	NCT02054806	Study of pembrolizumab (MK-3475) in participants with advanced solid tumors (MK-3475–028/KEYNOTE-2	Active, not recruiting	• Solid tumor (including advanced breast cancer, ER + HER2-)	• Biological: pembrolizumab (10 mg/kg every 2 weeks)	Interventional	Phase 1	• Intervention model: single group assignment• Masking: none (open label) • Primary purpose: treatment	• Best overall response using response. Evaluation criteria in solid tumors (RECIST version 1.1) • Progression-free survival (PFS) • Overall survival (OS) • Duration of response (DOR) in participants who achieve partial response (PR) or better, etc.	Tumor PD-L1 expression was assessed by immunohistochemistry at a central laboratory using a prototype assay (QualTek molecular laboratories, Goleta, CA, United States of America) (28) and the 22C3 antibody (Merck and co, Kenilworth, NJ, United States of America). PD-L1 expression was determined by combined positive score (CPS), defined as the number of PD-l1–positive cells (tumor cells, lymphocytes, and macrophages) divided by the total number of tumor cells, multiplied by 100. The specimen is considered to have positive PD-L1 expression when CPS ≥1	477 (25 breast cancer patients)	18 Years and older (adult, older adult)	All	Up to 24 months	4	1.1
Dirix, 2017	NCT01772004	Avelumab in metastatic or locally advanced solid tumors (JAVELIN solid tumor)	Active, not recruiting	• Breast cancer (advanced BC) • Solid tumor	• Biological: avelumab (10 mg/kg every 2 weeks)	Interventional	Phase 1	• Intervention model: single group assignment • Masking: none (open label) • Primary purpose: treatment	• Dose-limiting toxicity and treatment-emergent adverse events • Confirmed best overall response (BOR) • Immune-related best overall response (irBOR) and best overall response (BOR) • Overall survival time (OS) and progression-free survival (PFS) time • Level of PD-L1 tumor expression, etc.	Levels of PD-L1 protein were assessed by immunohistochemistry using a proprietary assay (PD-L1 IHC 73–10 pharmDx; Dako, Carpinteria, CA, United States of America) with an anti–PD-l1 rabbit monoclonal antibody. Expression was based on the percentages of tumor cells expressing PD-L1: 1 and 5% thresholds with any staining intensity and a 25% threshold with moderate to high staining. Additionally, dense aggregates of tumor-associated immune cells (identified as nonmalignant cells based on morphology) adjacent to tumor cells were assayed using a defined threshold of 10% of immune cells expressing PD-L1 at any staining intensity	1758 (168 breast cancer patients)	18 years and older (adult, older adult)	All	Up to 52 months	4	1.1
Nanda, 2016	NCT01848834	Study of pembrolizumab (MK-3475) in participants with advanced solid tumors (MK-3475–012/KEYNOTE-01	Active, not recruiting	• Breast cancer (advanced TNBC) • Solid tumor	• Biological: pembrolizumab (10 mg/kg every 2 weeks)	Interventional	Phase 1	• Allocation: nonrandomized • Intervention model: parallel assignment • Masking: none (open label) • Primary purpose: treatment	• Number of participants experiencing adverse events (AEs) • Number of participants discontinuing from study treatment due to an AE • Overall response evaluation criteria in solid tumors version 1.1 (RECIST1.1) response rate based on blinded independent central radiology (BICR) Review (cohorts A, B, and B2, C, and D) • Overall RECIST 1.1 response rate based on investigator assessment for cohorts A, B, C, D	PD-L1 was assessed in formalin-fixed, paraffin-embedded archival tumor samples at a central laboratory using a prototype immunohistochemistry assay and the 22C3 antihuman PD-1 antibody (Merck and Co., Kenilworth, NJ).24 positivity was defined as PD-L1 expression in the stroma or in ≥1% of tumor cells	297 (111 breast cancer patients)	18 years and older (adult, older adult)	All	Up to 31–34 months	4	1.1

CTC for AE version, Common Terminology Criteria for Adverse Events version.

RECIST version, Response Evaluation Criteria in Advanced Solid Tumors version.

TNBC, triple-negative breast cancer; ER+, estrogen receptor‒positive; HER2−, human epidermal growth factor receptor 2 negative.