Background: Immuno-oncology (IO) agents have demonstrated exceptional clinical benefit in patients with many tumor types, including melanoma and lung cancer. The PD-L1 inhibitor, atezolizumab, was recently FDA approved in combination with nab-paclitaxel for patients with PD-L1 positive triple-negative breast cancer (TNBC); however, single-agent PD-1/PD-L1 inhibitors demonstrate modest efficacy in breast cancer. The purpose of this study was to investigate the efficacy of IO agents in patients with metastatic breast cancer treated in phase I clinical trials.

Methods: We performed a retrospective analysis using a database of patients with metastatic breast cancer who received treatment with IO agents in phase I/Ib clinical trials at the University of Colorado Anschutz Medical Campus from January 1, 2012 to July 1, 2018. Abstracted data included patient demographics, baseline characteristics, and clinical outcomes.

Results: 208 patients with metastatic breast cancer were treated in phase I/Ib clinical trials; 43 were treated with an IO agent. The average age was 53 years old and 55.8% had hormone receptor-positive/HER2-negative breast cancer, 39.5% TNBC, and 4.6% HER2-positive disease. On average, patients received two prior lines of chemotherapy (range 0-7) in the metastatic setting. 31/43 patients (72.1%) received single agent or combination IO, and 12/43 (27.9%) received IO + chemotherapy. Median progression-free survival (PFS) was 2.3 months and median overall survival (OS) was 12.1 months in all patients. 9/43 (21%) of patients remained on study > 6 months and had a median PFS of 8.6 months. Patients remaining on study > 6 months were more likely to be treated with IO + chemotherapy compared to patients with a PFS < 6 months (77.8% v. 14.7%, p=0.0007). There was no difference in sites of metastasis, prior lines of chemotherapy, breast cancer subtype, absolute lymphocyte count, or LDH between patients with a PFS > 6 months compared to < 6 months.

Conclusions: A subset of patients with metastatic breast cancer treated in phase I clinical trials at our center with an IO agent had derived prolonged clinical benefit. The benefit was not limited to patients with TNBC and was associated with receipt of chemotherapy in combination with IO. Predictors of response to immunotherapy in breast cancer beyond PD-L1 expression remain uncharacterized, and further research is needed to identify these factors.

Citation Format: Jodi A. Kagihara, Jennifer A. Weiss, Andrew Nicklawsky, Dexiang Gao, Virginia F. Borges, Peter Kabos, Antonio Jimeno, Jennifer R. Diamond. Efficacy of immunotherapy agents in patients with metastatic breast cancer treated in phase I clinical trials [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2019 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(3 Suppl):Abstract nr A76.