LBA3 Atezolizumab with carboplatin as immune induction in metastatic lobular breast cancer: First results of the GELATO-trial

Abstract

Invasive lobular breast cancer (ILC) is a special histological breast cancer subtype for which endocrine treatment is effective, but options thereafter are limited. ILC appears to be a different disease entity than invasive breast cancer of no special type. Translational data suggested that a subgroup of ILC has high expression of immune-related genes. Preclinical data revealed that this subtype may be responsive to combined platinum and immune checkpoint blockade. Here we present the first results of a single-arm phase II trial of atezolizumab (atezo) after immune induction with carboplatin in metastatic (m)ILC. In the single-arm, multicenter GELATO-trial (NCT03147040), patients with mILC were treated with 12 cycles of carboplatin q1w (AUC 1.5 mg/mL·min) and atezo (1200 mg) q3w starting from the third cycle of carboplatin and continuing until progression or intolerability. Patients had received a maximum of 2 lines of palliative chemotherapy and were endocrine refractory in case of ER-positive tumors. The primary endpoint was progression-free survival at 24 weeks according to RECIST1.1. Following a Simon’s two-stage design, 22 patients, receiving at least 1 cycle of atezo, needed to be included in the first stage, of whom at least 3 patients had to be free of progression after 24 weeks to warrant further investigation in the second stage. Among 23 included evaluable patients, 4 patients were free of progression at 24 weeks, meeting the primary endpoint of the first stage of the trial. 1 patient has an ongoing response and 2 patients have started treatment but have not yet reached an endpoint. 4 out of these 21 patients had a partial response resulting in an objective response rate of 19% and 2 patients had stable disease, resulting in a clinical benefit rate of 29%. 4 of the patients with clinical benefit had triple negative (TN)-ILC, whereas in total 5 out of 23 patients had TN-ILC. Stromal tumor-infiltrating lymphocytes were not associated with clinical benefit. PD-L1 and CD8 will be presented at the meeting. This is the first clinical immunotherapy trial executed exclusively in mILC. We show a clear efficacy signal of PDL1-blockade in combination with carboplatin in mILC, mainly in patients with TN-ILC.