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Long-term Clinical Outcomes and Biomarker Analyses of Atezolizumab Therapy for Patients With Metastatic
Leisha A Emens1,2, Cristina Cruz3, Joseph Paul Eder4
1Bloomberg-Kimmel Institute for Cancer Immunotherapy, Department of Oncology, Johns Hopkins University, Baltimore, Maryland.
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.
Insights
Atezolizumab is well tolerated in metastatic triple-negative breast cancer (mTNBC), showing durable clinical benefit, especially in first-line treatment and for patients with high PD-L1 expression on immune cells.
Area of Science:
- Oncology
- Immunotherapy
Background:
- Atezolizumab, an anti-PD-L1 therapy, is effective in various cancers.
- Its role in metastatic triple-negative breast cancer (mTNBC) was previously unreported.
Purpose of the Study:
- To assess the safety and clinical activity of atezolizumab monotherapy in mTNBC patients.
- To identify biomarkers associated with treatment response.
Main Methods:
- Phase 1, open-label, multicohort study of atezolizumab in 116 mTNBC patients.
- Treatment administered intravenously every 3 weeks.
- Safety, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were evaluated.
Main Results:
- Atezolizumab was well-tolerated, with most adverse events being low-grade.
- Higher ORRs were observed in first-line patients (24%) compared to later lines (6%).
- Patients with PD-L1 expression on immune cells (≥1%) showed improved ORRs and OS.
Conclusions:
- Single-agent atezolizumab is a safe and effective option for mTNBC.
- Durable clinical benefits were observed, particularly in earlier lines of therapy and in patients with PD-L1 expression.
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