Adding Dual Immune Blockade to Chemotherapy for HER2-Negative Breast Cancer

By: Julia Fiederlein Cipriano
Posted: Monday, February 13, 2023

The addition of the PD-1 inhibitor cemiplimab-rwlc and the LAG-3 inhibitor REGN3767 to neoadjuvant chemotherapy with paclitaxel resulted in improved rates of pathologic complete response in patients with early-stage, high-risk, HER2-negative breast cancer, according to Claudine Isaacs, MD, of Georgetown University, Washington, DC, and colleagues. The results of the multicenter phase II I-SPY2 trial, which were presented during the 2022 San Antonio Breast Cancer Symposium (SABCS; GS5-03), also identified a subgroup with hormone receptor–positive disease who might likely benefit from this combination regimen.

Patients with HER2-negative disease whose tumors were 2.5 cm or larger received paclitaxel alone (n = 357) or in combination with cemiplimab and REGN3767 (n = 73); both regimens were followed by doxorubicin plus cyclophosphamide. The combination regimen was eligible to graduate in three prespecified biomarker signatures: all HER2-negative, triple-negative, and hormone receptor–positive. The investigators assessed response predictive subtypes using pretreatment gene-expression data and a 53-gene signature.

In the all HER2-negative, triple-negative, and hormone receptor–positive biomarker subgroups, the estimated pathologic complete response rates were 44.6%, 59.3%, and 37.0% with the combination regimen and 21.1%, 29.1%, and 14.5% with paclitaxel alone, respectively; based on these data, the combination regimen graduated in all three biomarker signatures. The predictive probability of success in a phase III trial was 0.960 in the all HER2-negative subgroup, 0.973 in the triple-negative subgroup, and 0.939 in the hormone receptor–positive subgroup. Of note, hypothyroidism (30.8%), adrenal insufficiency (19.2%), hyperthyroidism (14.1%), pneumonitis (1.3%), and hepatitis (3.8%) were reported with the combination regimen.

A total of 40 and 32 patients treated with the combination regimen were predicted to be immune-positive and immune-negative, respectively. In the hormone receptor–positive subgroup, more immune-positive patients achieved a pathologic complete response than their immune-negative counterparts (91.0% vs. 28.0%).

Disclosure: For full disclosures of the study authors, visit sabcs.org.

2022 San Antonio Breast Cancer Symposium

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