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Original Investigation
January 2019

Long-term Clinical Outcomes and Biomarker Analyses of Atezolizumab Therapy for Patients With Metastatic Triple-Negative Breast Cancer: A Phase 1 Study

Author Affiliations
  • 1Bloomberg-Kimmel Institute for Cancer Immunotherapy, Department of Oncology, Johns Hopkins University, Baltimore, Maryland
  • 2now with Department of Medicine and UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh
  • 3Medical Oncology Department, Vall d’Hebron Institute of Oncology (VHIO), Vall d’Hebron University Hospital, Barcelona, Spain
  • 4Department of Medicine (Oncology), Yale Cancer Center, New Haven, Connecticut
  • 5Comprehensive Cancer Centers of Nevada, University of Nevada Las Vegas School of Medicine, Las Vegas
  • 6The Angeles Clinic and Research Institute, Los Angeles, California
  • 7Department of Medicine,Dana-Farber Cancer Institute, Boston, Massachusetts
  • 8Department of Medicine, Hematology/Oncology, Massachusetts General Hospital, Boston
  • 9Section of Hematology/Oncology, University of Chicago, Chicago, Illinois
  • 10Department of Medical Oncology, Centre Léon-Bérard, Lyon, France
  • 11Department of Medical Oncology, Institut Claudius Regaud, IUCT-Oncopole, Toulouse, France
  • 12HonorHealth Research Institute, Scottsdale, Arizona
  • 13Ventana Medical Systems, Inc, Tucson, Arizona
  • 14Genentech, Inc, South San Francisco, California
  • 15now with Bellicum Pharmaceuticals, Inc, South San Francisco, California
  • 16Centre for Experimental Cancer Medicine, Barts Cancer Institute, Queen Mary University of London, London, England
JAMA Oncol. 2019;5(1):74-82. doi:10.1001/jamaoncol.2018.4224
Key Points

Question  Is single-agent atezolizumab therapy safe and does it provide clinical benefit in patients with metastatic triple-negative breast cancer (mTNBC)?

Findings  In this phase 1 study of 116 patients with mTNBC, the safety profile was consistent with that of atezolizumab in other tumor types. With a median follow-up of longer than 2 years, patients with an objective response to atezolizumab had a durable clinical response, and patients with higher tumor immune cell infiltration had better clinical outcomes.

Meaning  Single-agent atezolizumab was well tolerated and showed durable clinical activity in patients with mTNBC.


Importance  Atezolizumab (anti–programmed cell death ligand 1 [PD-L1]) is well tolerated and clinically active in multiple cancer types. Its safety and clinical activity in metastatic triple-negative breast cancer (mTNBC) has not been reported.

Objective  To evaluate the safety, clinical activity, and biomarkers associated with the use of single-agent atezolizumab in patients with mTNBC.

Design, Setting, and Participants  Women with mTNBC (defined by investigator assessment) were enrolled between January 2013 and February 2016 in a multicohort open-label, phase 1 study at US and European academic medical centers. Median follow-up was 25.3 months (range, 0.4-45.6 months). Eligible patients regardless of line of therapy had measurable disease by Response Evaluation Criteria in Solid Tumors, version 1.1; Eastern Cooperative Oncology Group performance status of 0 to 1; and a representative tumor sample for assessment of immune cell (IC) PD-L1 expression.

Interventions  Atezolizumab was given intravenously every 3 weeks until unacceptable toxic effects or loss of clinical benefit.

Main Outcomes and Measures  Primary outcome was safety and tolerability. Activity and exploratory outcomes included objective response rate (ORR), duration of response, progression-free survival (PFS), and overall survival (OS). Outcomes were assessed in all patients and in key patient subgroups.

Results  Among 116 evaluable patients (median age, 53 years [range, 29-82 years]), treatment-related adverse events occurred in 73 (63%); 58 (79%) were grade 1 to 2. Most adverse events occurred within the first treatment year. The ORRs were numerically higher in first-line (5 of 21 [24%]) than in second-line or greater patients (6 of 94 [6%]). Median duration of response was 21 months (range, 3 to ≥38 months). Median PFS was 1.4 (95% CI, 1.3-1.6) months by RECIST and 1.9 (95% CI, 1.4-2.5) months by irRC. In first-line patients, median OS was 17.6 months (95% CI, 10.2 months to not estimable). Patients with PD-L1 expression of at least 1% tumor-infiltrating ICs had higher ORRs and longer OS (12% [11 of 91]; 10.1 [95% CI, 7.0-13.8] months, respectively) than those with less than 1% ICs (0 of 21; 6.0 [95% CI, 2.6-12.6] months, respectively). High levels of ICs (>10%) were independently associated with higher ORRs and longer OS.

Conclusions and Relevance  Single-agent atezolizumab was well tolerated and provided durable clinical benefit in patients with mTNBC with stable or responding disease and in earlier lines of treatment.

Trial Registration  ClinicalTrials.gov identifier: NCT01375842