Excellent Responses to Atezolizumab in Small Subset of Women with Triple-Negative Breast Cancer

Washington, DC—Preliminary data show excellent and durable responses to atezolizumab (Tecentriq) in 10% of women with triple-negative breast cancer, one of the most aggressive and difficult-to-treat cancers. Of the responders to atezolizumab, 100% were alive at 1 year compared with only 38% of nonresponders. The trick will be to identify which women will respond to immune checkpoint inhibitor therapy. Thus far, no biomarkers for response have been identified.

This represents the largest cohort of patients with metastatic breast cancer who received immunother­apy to date, and it is the first study to report data on survival for this subpopulation.

“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 investigator Peter Schmid, MD, PhD, FRCP, Director, Breast Cancer, St Bartholomew Hospital, London, England, who presented the study results at the 2017 American Association for Cancer Research meeting.

This phase 1 study included a cohort of 115 patients with metastatic triple-negative breast cancer who received intravenous atezoliz­umab every 3 weeks at 15 mg/kg, 20 mg/kg, or a flat dose of 1200 mg. Overall, 65% of the patients had visceral metastasis, and 30% had bone metastasis. Patients had received a median of 7 previous systemic therapies, and 58% received third-line therapy or more.

Atezolizumab, a selective PD ligand 1 (PD-L1) inhibitor, is currently approved by the FDA for the treatment of patients with metastatic non–small-cell lung cancer and for patients with locally advanced or metastatic urothelial bladder cancer.

The objective response rate according to Response Evaluation Criteria in Solid Tumors criteria was 10% overall, and 13% in patients who had PD-L1 expression >5%. The overall response rate was 26% in patients who received atezoliz­umab as first-line treatment and 11% for the second-line group. Disease control (response plus stable disease) was achieved in 17% of patients overall, and in 32% of those who received first-line treatment.

“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, the duration of response is substantially longer than what has been seen with any other treatment to date for this population.”

The median overall survival in the study was 9.3 months. The 1-year overall survival was 41%, and the 2-year survival was 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,” Dr Schmid emphasized.

With extended follow-up of 15 months, atezolizumab continues to be generally well-tolerated.

Exploratory analysis suggested that higher response rates were potentially associated with higher levels of tumor-infiltrating lymphocytes, higher 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, adding that, “we cannot use PD-L1 expression as a biomarker for atezolizumab.”

The phase 3 IMpassion130 trial is evaluating the combination of atezoliz­umab plus chemotherapy in the first-line setting for triple-negative breast cancer. The goal is to exploit the effects of immunotherapy with chemotherapy in this patient population.

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