SAN ANTONIO, TX—Avelumab has an acceptable safety profile in patients with metastatic breast cancer (mBC); and despite a modest objective response rate (ORR) in an overall unselected cohort of patients with metastatic breast cancer, avelumab showed signs of greater clinical activity in specific subsets of patients. These study findings were presented at the San Antonio Breast Cancer Symposium.1

The programmed death-1 receptor (PD-1) and its ligand are key therapeutic targets in the reactivation of the immune response against cancer. Avelumab is a fully human anti-PD-L1 IgG1 antibody that binds to PD-L1 to inhibit PD-1/PD-L1 interactions while leaving the PD-1/PD-L2 pathway intact. In patients with triple-negative breast cancer (TNBC), presence of programmed death-1 receptor ligand (PD-L1) expressing immune cells within the tumor may be associated with clinical responses to avelumab.

This study was a phase Ib cohort expansion from a clinical study involving patients with lung, gastric, ovarian, bladder, and other malignancies. This cohort included 168 patients (1 male, 167 female) with histologically confirmed mBC refractory to or progressing after standard-of-care therapy, age 31 to 81 years (median age, 55 years). Tumor sites included ductal (94; 56.0%), lobular (6; 3.6%), carcinoma NOS (14; 8.3%), or other (54; 32.1%). ECOG performance status was 0 (49.4%) or 1 (50.6%). Patients had received 3 or more prior lines of therapy that included taxane and anthracycline, and biopsy or surgical specimen was obtained 90 days prior to first administration of avelumab.

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Patients received avelumab 10 mg/kg every 2 weeks until confirmed progression, unacceptable toxicity, or any criterion for withdrawal occurred. Select assessments included safety and tolerability, BOR by RECIST 1.1 criteria, and PD-L1 expression status by immunohistochemical staining at various cut-offs. Median duration of treatment was 8 weeks (range 2 to 50 weeks), and 9 patients (5.4%) remained on avelumab.

Any grade treatment-related adverse event (TEAE) occurred in 115 patients (68.5%); those TEAEs occurring in more than 10% of patients included fatigue (32; 19.0%), infusion-related reactions (24; 14.3%), and nausea (22; 13.1%). TEAEs grade 3 or higher occurred in 24 patients (13.7%), including fatigue (3; 1.8%), increased GGT (3; 1.8%), autoimmune hepatitis (3; 1.8%), anemia (3; 1.8%), and arthralgia (1; 0.6%). There were 2 treatment-related deaths (acute liver failure, respiratory distress).

Unconfirmed objective response rate (ORR) in the entire cohort was 5.4% (9 patients; 95% CI: 2.5, 9.9), with 1 complete response (CR) and 7 partial responses (PRs). Nine patients remained on treatment at the data cut-off. Stable disease was observed in an additional 39 patients (23.2%), for an overall disease control rate of 29.2%. Evidence of tumor reduction by 30% or more was seen in 16 patients (9.5%). All biomarker subgroups included responders, including 5 of 58 PRs in TNBC (8.6%; 95% CI: 2.9, 19.0). PD-L1 expression was evaluable in 136 patients. Among all patients with PD-L1 expressing immune cells within the tumor, 33.3% (4 of 12) had PRs. In patients with TNBC who had PD-L1+ immune cells within the tumor, 44.4% (4 of 9) had PRs, compared with 2.6% (1 of 39) for TNBC and PD-L1– immune cells.

Further analyses of PD-L1 expression and clinical activity of avelumab in metastatic breast cancer are ongoing.


1. Dirix LY, Takacs I, Nikolinakos P, et al. Avelumab (MSB0010718C), an anti-PD-L1 antibody, in patients with locally advanced or metastatic breast cancer: A phase Ib JAVELIN solid tumor trial. Oral presentation at: San Antonio Breast Cancer Symposium; December 9-12, 2015; San Antonio, TX.