Long-Term Outcomes With Anti–PD-L1 Treatment in Metastatic Triple-Negative Breast Cancer
In a long-term follow-up of a phase I trial reported in JAMA Oncology, Emens et al found that single-agent atezolizumab (Tecentriq) produced enduring benefit in patients with metastatic triple-negative breast cancer after stable or responding disease and in first-line treatment.
Study Details
In the study, performed at sites in the United States and Europe, 116 evaluable patients irrespective of line of therapy received atezolizumab every 3 weeks (at 15 or 20 mg/kg or at a 1,200-mg flat dose) initially for up to 16 cycles or 1 year. A protocol amendment allowed for treatment beyond 16 cycles/1 year and for retreatment of patients who had discontinued therapy, regardless of disease status. Treatment beyond RECIST progression until loss of clinical benefit was allowed, according to investigator discretion.
Treatment Outcomes
Median follow-up was 25.3 months. Median treatment duration was 2.1 months (range = 0–45.6 months), with a median of 4 cycles (range = 1–58 cycles). Overall, 16 patients received treatment for 16 cycles or for 1 year; 10 continued to receive treatment at the time of analysis.
Overall response occurred in 5 (24%) of 21 patients receiving first-line treatment and in 6 (6%) of 94 receiving second-line treatment or greater. Median duration of response was 21 months (range = 3–≥ 38 months). Median progression-free survival was 1.4 months on RECIST and 1.9 months on immune-related response criteria. Median overall survival was 17.6 months in patients receiving first-line therapy and 7.3 months in those receiving later lines of treatment. Among 99 efficacy-evaluable patients who survived for at least 6 weeks, 9 (82%) of 11 patients with complete or partial response by RECIST were still alive at time of analysis. Among 15 patients with stable disease, median overall survival was 15.9 months. Among 73 with progressive disease, median overall survival was 7.3 months.
Programmed cell death ligand 1 (PD-L1) expression of ≥ 1% tumor-infiltrating immune cells was associated with response in 11 (12%) of 91 patients and median overall survival of 10.1 months; expression < 1% was associated with response in 0 of 21 patients and median overall survival of 6.0 months.
Adverse Events
Treatment-related adverse events of any grade occurred in 63% of patients, with most (79%) being grade 1 to 2. Grade 3 or 4 treatment-related adverse events occurred in 13 patients (11%), including grade 4 hyperglycemia and grade 4 pneumonitis. Grade 3 or 4 treatment-related adverse events of special interest included grade 3 pruritic rash, lichen planus, and adrenal insufficiency; and grade 4 pneumonitis. Two patients died due to treatment-related adverse events—one due to pulmonary hypertension and one due to death not otherwise specified in a hospitalized patient.
The investigators concluded, “Single-agent atezolizumab was well tolerated and provided durable clinical benefit in patients with [metastatic triple-negative breast cancer] with stable or responding disease and in earlier lines of treatment.”
The study was sponsored by F. Hoffmann-La Roche Ltd.
Leisha A. Emens, MD, PhD, of the University of Pittsburgh, UPMC Hillman Cancer Center, is the corresponding author for the JAMA Oncology article.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
