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

• Published in: JAMA oncology Vol. 5; no. 1; p. 74
• Main Authors: Emens, Leisha A, Cruz, Cristina, Eder, Joseph Paul, Braiteh, Fadi, Chung, Cathie, Tolaney, Sara M, Kuter, Irene, Nanda, Rita, Cassier, Philippe A, Delord, Jean-Pierre, Gordon, Michael S, ElGabry, Ehab, Chang, Ching-Wei, Sarkar, Indrani, Grossman, William, O'Hear, Carol, Fassò, Marcella, Molinero, Luciana, Schmid, Peter
• Format: Journal Article
• Language: English
• Published: United States 01.01.2019
• Subjects: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized - adverse effects; Antibodies, Monoclonal, Humanized - therapeutic use; Antineoplastic Agents, Immunological - adverse effects; Antineoplastic Agents, Immunological - therapeutic use; B7-H1 Antigen - antagonists & inhibitors; B7-H1 Antigen - immunology; Disease Progression; Europe; Female; Humans; Middle Aged; Neoplasm Metastasis; Progression-Free Survival; Time Factors; Triple Negative Breast Neoplasms - drug therapy; Triple Negative Breast Neoplasms - immunology; Triple Negative Breast Neoplasms - mortality; Triple Negative Breast Neoplasms - pathology; United States; United States; Europe
• ISSN: 2374-2445
• DOI: 10.1001/jamaoncol.2018.4224

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. To evaluate the safety, clinical activity, and biomarkers associated with the use of single-agent atezolizumab in patients with mTNBC. 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. Atezolizumab was given intravenously every 3 weeks until unacceptable toxic effects or loss of clinical benefit. 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. 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. 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. ClinicalTrials.gov identifier: NCT01375842.