PURPOSE: Agents targeting programmed death receptor 1 (PD-1) or its ligand (PD-L1)
have shown antitumor activity in the treatment of metastatic breast cancer (MBC).
The aim of this study was to assess the activity of avelumab, a PD-L1 inhibitor, in
patients with MBC. METHODS: In a phase 1 trial (JAVELIN Solid Tumor; NCT01772004),
patients with MBC refractory to or progressing after standard-of-care therapy received
avelumab intravenously 10 mg/kg every 2 weeks. Tumors were assessed every 6 weeks
by RECIST v1.1. Adverse events (AEs) were graded by NCI-CTCAE v4.0. Membrane PD-L1
expression was assessed by immunohistochemistry (Dako PD-L1 IHC 73-10 pharmDx). RESULTS:
A total of 168 patients with MBC, including 58 patients with triple-negative breast
cancer (TNBC), were treated with avelumab for 2-50 weeks and followed for 6-15 months.
Patients were heavily pretreated with a median of three prior therapies for metastatic
or locally advanced disease. Grade >/= 3 treatment-related AEs occurred in 13.7% of
patients, including two treatment-related deaths. The confirmed objective response
rate (ORR) was 3.0% overall (one complete response and four partial responses) and
5.2% in patients with TNBC. A trend toward a higher ORR was seen in patients with
PD-L1+ versus PD-L1- tumor-associated immune cells in the overall population (16.7%
vs. 1.6%) and in the TNBC subgroup (22.2% vs. 2.6%). CONCLUSION: Avelumab showed an
acceptable safety profile and clinical activity in a subset of patients with MBC.
PD-L1 expression in tumor-associated immune cells may be associated with a higher
probability of clinical response to avelumab in MBC.
