Avelumab, an anti-PD-L1 antibody, in patients with locally advanced or metastatic breast cancer: a phase 1b JAVELIN Solid Tumor study

Luc Y. Dirix, Istvan Takacs, Guy Jerusalem, Petros Nikolinakos, Hendrik Tobias Arkenau, Andres Forero-Torres, Ralph Boccia, Marc E. Lippman, Robert Somer, Martin Smakal, Leisha A. Emens, Borys Hrinczenko, William Edenfield, Jayne Gurtler, Anja von Heydebreck, Hans Juergen Grote, Kevin Chin, Erika P. Hamilton

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1-16
Number of pages16
JournalBreast Cancer Research and Treatment
DOIs
StateAccepted/In press - Oct 23 2017

Keywords

  • Avelumab
  • Metastatic breast cancer
  • PD-L1
  • Second-line
  • Triple-negative breast cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Dirix, L. Y., Takacs, I., Jerusalem, G., Nikolinakos, P., Arkenau, H. T., Forero-Torres, A., Boccia, R., Lippman, M. E., Somer, R., Smakal, M., Emens, L. A., Hrinczenko, B., Edenfield, W., Gurtler, J., von Heydebreck, A., Grote, H. J., Chin, K., & Hamilton, E. P. (Accepted/In press). Avelumab, an anti-PD-L1 antibody, in patients with locally advanced or metastatic breast cancer: a phase 1b JAVELIN Solid Tumor study. Breast Cancer Research and Treatment, 1-16. https://doi.org/10.1007/s10549-017-4537-5