FDA Approval Summary: Pembrolizumab for Neoadjuvant and Adjuvant Treatment of Patients with High-Risk Early-Stage Triple-Negative Breast Cancer

Abstract

On July 26, 2021, the Food and Drug Administration granted approval to pembrolizumab in combination with chemotherapy for neoadjuvant treatment and then continued as a single agent for adjuvant treatment following surgery for patients with high-risk, early-stage triple negative breast cancer (TNBC). Approval was based on results from KEYNOTE-522, an ongoing randomized (2:1) trial evaluating pembrolizumab or placebo in combination with chemotherapy for neoadjuvant treatment and then as a single agent for adjuvant treatment. The co-primary endpoints were pathological complete response (pCR) rate and event free survival (EFS). The trial demonstrated an improvement in pCR and EFS in the pembrolizumab arm compared to the control arm. The number of patients who experienced an EFS event was 123 (16%) and 93 (24%), respectively (HR: 0.63, 95% CI: 0.48-0.82, p=0.00031). Patients on the pembrolizumab arm experienced EFS benefit regardless of tumor PD-L1 status. The absolute pCR rate improvement with the addition of pembrolizumab was 7.5% (95% CI: 1.6%, 13.4%). Among patients receiving pembrolizumab, 44% experienced an immune-related adverse reaction. This article summarizes FDA’s review of pembrolizumab and the data supporting the favorable benefit-risk assessment.

Targeting the Oxytocin Receptor for Breast Cancer Management: A Niche for Peptide Tracers

“…9,18 Pembrolizumab, a humanized monoclonal anti-programmed cell death protein 1 (PD1) antibody, is used as a neoadjuvant and adjuvant for treating patients with high-risk early-stage TNBC. 19,20 According to the "5-year relative survival percentage" reported by the U.S. National Cancer Institute, the highest survival pattern was observed in women with luminal A subtype (94.4%), followed by the luminal B subtype (90.7%), HER2 subtype (84.8%), and finally TNBC (77.1%). 9 Although mortality has decreased due to early detection and increasing therapeutic options, almost 30% of patients diagnosed with early stages of breast cancer still develop recurrent or metastatic diseases, 9 with 5-year survival rates in those patients of only 27%.…”

Mammary carcinoma: Comparative oncology between small animals and humans—New therapeutic tools

“…Antibodies that target the immunoregulatory PD‐1 (programmed cell death‐1 receptor)/PD‐L1 (programmed death ligand‐1) axis, have recently shown clinical efficiency for triple‐negative BCs. The new standard of care for high‐risk, early triple‐negative BCs is neoadjuvant chemotherapy + pembrolizumab (an anti‐PD‐1 antibody) followed by adjuvant pembrolizumab (Emens & Loi, 2023; Shah et al, 2022). For metastatic triple‐negative BCs that significantly express PD‐L1, pembrolizumab is used in combination with chemotherapy (Cortes et al, 2022).…”

“…The new standard of care for high-risk, early triple-negative BCs is neoadjuvant chemotherapy + pembrolizumab (an anti-PD-1 antibody) followed by adjuvant pembrolizumab (Emens & Loi, 2023;Shah et al, 2022). For metastatic triple-negative BCs that significantly express PD-L1, pembrolizumab is used in combination with chemotherapy (Cortes et al, 2022).…”

Monoclonal Antibodies in Cancer Immunotherapy

“…PD-L1 is expressed in a variety of tumor cells, and its combination with PD-1 of T cells contributes to the immune escape mechanism of tumors. The monoclonal antibodies developed using this mechanism include: nivolumab, pembrolizumab, toripalimab, sintilimab approved in 2018, and Approved durvalizuma, and atezolizumab approved in 2020 [5][6][7][8][9][10].…”