Preliminary data show excellent and durable responses to atezolizumab in 10% of women with triple-negative breast cancer (TNBC), one of the most aggressive and difficult cancers to treat. One hundred percent of responders to atezolizumab were alive at 1 year compared with 38% of nonresponders. The trick will be to identify which women will respond to immune checkpoint inhibitor therapy. Thus far, there are no biomarkers for response.
These data represent the largest cohort of patients with metastatic breast cancer treated with immunotherapy to date, and the study is the first to report data on survival for this subgroup.
“The most significant finding is the difference in overall survival between patients who responded to atezolizumab and patients who did not respond. While all responders were alive after 1 year, the 1-year survival rate for nonresponders was only 38%,” said lead author Peter Schmid, MD, PhD, director of the St. Bartholomew’s Breast Centre at St. Bartholomew’s Hospital and Barts Cancer Institute, London, UK. He presented results at the 2017 Annual Meeting of AACR.
The phase 1 study included a cohort of 115 patients with metastatic TNBC treated with atezolizumab IV every 3 weeks at 15 or 20 mg/kg or a flat dose of 1200 mg. Sixty-five percent had visceral metastasis and 30% had bone metastasis. Patients had been treated with a median of 7 prior systemic therapies; 58% were being treated as third-line or higher.
Atezolizumab, a selective PD-L1 inhibitor, is currently approved by the FDA for the treatment of metastatic non–small cell lung cancer and for locally advanced or metastatic urothelial bladder cancer.
Objective response rate (ORR) according to RECIST was 10% overall and 13% in the group with PD-L1 >5%; ORR was 26% in patients treated in the first-line group and 11% for those in the second-line group. Disease control (response plus stable disease) was achieved in 17% of patients overall and 32% of those treated first-line.
“Atezolizumab did not benefit a relatively large proportion of patients who progressed relatively quickly,” Dr Schmid acknowledged. “But among responders, median duration of response was 21.1 months. In the context of a median overall survival of 9 to 12 months in this disease, duration of response is substantially longer than what has been seen with any other treatment to date for this population.”
Median overall survival in the study was 9.3 months in all patients. One-year overall survival was 41%, and at 2 years, 22%. Among responders, 1- and 2-year survival was 100% versus 11% for nonresponders.
“Overall survival was substantially longer than what we see with other therapies in this disease,” he emphasized.
With extended follow-up of 15 months, atezolizumab continues to be generally well tolerated.
Exploratory analysis suggested that higher response rates seemed to be associated with higher levels of tumor-infiltrating lymphocytes, higher levels of CD8 T cells, and, “to a lesser extent,” higher PD-L1 expression.
“Patients with higher and lower PD-L1 expression benefited from atezolizumab,” Dr Schmid stated. “We cannot use PD-L1 expression as a biomarker for atezolizumab.”
The phase 3 IMpassion trial is evaluating the combination of atezolizumab plus chemotherapy in the first-line setting for TNBC. The idea is to exploit the effects of immunotherapy with chemotherapy.
