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Clinical Trial
. 2018 Feb;167(3):671-686.
doi: 10.1007/s10549-017-4537-5. Epub 2017 Oct 23.

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  1 , Istvan Takacs  2 , Guy Jerusalem  3 , Petros Nikolinakos  4 , Hendrik-Tobias Arkenau  5   6 , Andres Forero-Torres  7 , Ralph Boccia  8 , Marc E Lippman  9 , Robert Somer  10 , Martin Smakal  11 , Leisha A Emens  12 , Borys Hrinczenko  13 , William Edenfield  14 , Jayne Gurtler  15 , Anja von Heydebreck  16 , Hans Juergen Grote  16 , Kevin Chin  17 , Erika P Hamilton  18
Affiliations
Clinical Trial

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 et al. Breast Cancer Res Treat. 2018 Feb.

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.

Keywords: Avelumab; Metastatic breast cancer; PD-L1; Second-line; Triple-negative breast cancer.

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Conflict of interest statement

GJ Reports honoria from Novartis, Celgene, and Roche; consulting/advisory roles for Novartis and Celgene; research funding from Novartis, MSD, and Roche; travel, accommodations, expenses from Novartis, Roche, and GSK. AFT reports research funding (to institution) from Pfizer. RB reports honoraria from Amgen, Celgene, AstraZeneca, and Tesaro; consulting/advisory role, speaker’s bureau fees, and travel, accommodations, and expenses for Heron Therapeutics. ML reports a leadership role and stock or other ownership for Seattle Genetics, Oncology analytics, and Geneyus. LE reports travel, accommodations, or expenses from Bayer Pharmaceuticals; consulting/advisory roles for Celgene, Vaccinex, Amgen, AstraZeneca, Syndax, Peregrine, eTHeRNA, Bayer, Molecuvax, and Gritstone; research funding from Genentech, Roche, EMD Serono, MaxCyte, MSD, AstraZeneca, Aduro Biotech, and Corvus; and is an SGE to the FDA. BH reports consulting/advisory roles for Bayer, Gilead, and Biotheranostics and research funding from EMD Serono, MedImmune, and AstraZeneca. WE participated in speakers’ bureau for Astellas and Medivation. JG reports research funding from EMD Serono. AvH and HJG are employees at Merck KGaA, Darmstadt, Germany. KC is an employee of EMD Serono, Inc., a subsidiary of Merck KGaA, Darmstadt, Germany. EH reports research funding (to institution) from Sarah Cannon Research Institute. All other authors have nothing to disclose.

Figures

Fig. 1
Fig. 1
Time to and duration of response for patients with confirmed or unconfirmed responses
Fig. 2
Fig. 2
Best change in target lesions from baseline in 140 evaluable patients with baseline tumor assessment and ≥ 1 post-baseline assessment
Fig. 3
Fig. 3
Percent change in target lesions from baseline in 46 evaluable patients with TNBC with baseline tumor assessment and ≥ 1 post-baseline assessment
See this image and copyright information in PMC

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