Long-term Clinical Outcomes and Biomarker Analyses of Atezolizumab Therapy for Patients With Metastatic Triple-Negative Breast Cancer

Abstract

ClinicalTrials.gov identifier: NCT01375842.

Breast Cancer, Version 3.2020, NCCN Clinical Practice Guidelines in Oncology

“…116 PD-L1-positive expression in tumor-infiltrating immune cells of 1% or more has been associated with a better outcome with PD-L1 inhibitor treatment. 117 A subsequent 18-month follow-up analysis confirmed PFS and OS benefits among those with PD-L1-expressing tumors. 118 Atezolizumab plus albumin-bound paclitaxel is included as a preferred option for those with advanced triple-negative breast cancer with PD-L1 expression in $1% tumor-infiltrating immune cells.…”

Immune checkpoint inhibitor‐associated pituitary‐adrenal dysfunction: A systematic review and meta‐analysis

“…The rate of all‐grade adrenal insufficiency ranged from 0% to 64%, and the rate of serious‐grade adrenal insufficiency ranged from 0% to 33.3%. One study did not report the number of events; across the other studies, 289 cases of any‐grade adrenal insufficiency were observed among 12 295 patients, and 176 cases of serious‐grade adrenal insufficiency were observed among 22 103 patients. Using a random effects model, the rates of all‐grade and serious‐grade adrenal insufficiency were 2.43% (95% CI, 1.73%‐3.22%) and 0.15% (95% CI, 0.05%‐0.29%), respectively (Table ).…”

A phase 2 clinical trial assessing the efficacy and safety of pembrolizumab and radiotherapy in patients with metastatic triple‐negative breast cancer

“…6,7 Approximately 47% of patients (8 of 17 patients) developed PD prior to week 13 and 53% (9 of 17 patients) were radiographically assessed for response, the majority of whom were exposed to a large number of prior therapies, thereby reflecting the advanced stage of disease among and poor prognosis of the study population. The primary purpose of the current study was to assess the safety and efficacy of pembrolizumab and RT using National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.0) and RECIST (version 1.1).…”

“…In the intention-to-treat cohort, the ORR of 17.6% (3 of 17 patients; 95% CI, 4.7%-44.2%) in a population that was unselected for PD-L1 status was higher than responses reported with checkpoint blockade monotherapy in previously treated patients with mTNBC. 6,7 Approximately 47% of patients (8 of 17 patients) developed PD prior to week 13 and 53% (9 of 17 patients) were radiographically assessed for response, the majority of whom were exposed to a large number of prior therapies, thereby reflecting the advanced stage of disease among and poor prognosis of the study population. A notable finding of the current study was that the ORR among the 9 patients who were evaluated according to RECIST at week 13 was 33% (3 of 9 patients), with all 3 responders achieving CRs in the unirradiated sites of disease.…”

“…1,2 High levels of tumor-infiltrating lymphocytes, increased expression of programmed death-ligand 1 (PD-L1), and a high tumor mutational burden may render patients with TNBC sensitive to programmed cell death protein 1 (PD-1)-directed immune modulation [3][4][5] ; however, modest response rates to checkpoint blockade monotherapy in the second-line palliative setting and beyond of 5% to 6% indicate that rational combinations are needed to augment sensitivity. 6,7 Pembrolizumab is a humanized monoclonal immunoglobulin (Ig) G4-k antibody that binds to PD-1 and prevents binding by PD-L1 and PD-L2. Pembrolizumab monotherapy has demonstrated a response rate of 4.7% in previously treated patients with mTNBC regardless of PD-L1 status.…”