Atezolizumab Demonstrates Long-Term Responses in Subset of TNBC

Peter Schmid, MD, PhD

Peter Schmid, MD, PhD

According to the results of a phase I study of single agent anti-PD-L1 atezolizumab (Tecentriq) in metastatic triple-negative breast cancer (mTNBC), ten percent of patients showed impressive long-term survival, although researchers said that aside from some biomarker evidence, it’s yet unclear why the drug was more effective in this subset of patients.

Results of the study were presented this week at the AACR Annual Meeting 2017 by lead author Peter Schmid, MD, PhD, director of the St. Bartholomew’s Breast Centre at St. Bartholomew’s Hospital and Barts Cancer Institute in London.

“We saw that higher response was associated with higher TILs, with higher CD8 T cells, and to a lesser degree with higher PD-L1 on immune cells, but all of these markers weren’t black and white in a way that we can say we can select all the responders based on this or can deselect a certain group,” Schmid said.

The study included 112 patients evaluable for response, and of those, 11 responded to treatment (complete and partial responses). Both 1- and 2-year overall survival (OS) rates for these responders were 100%; for nonresponders, OS rates were 33% and 11% respectively. Treatment-related grade 3 or 4 adverse events (AEs) were reported for 11% of patients, and AEs contributed to discontinuation of treatment in 3% of cases, Schmid said.

Whereas Schmid expressed confidence that the results suggested strong potential for the role of immunotherapy in breast cancer, he was challenged on that point during the press conference by Elaine Schattner, MD, an oncology contributor for Forbes Magazine, who stated that the small subset of patients who experienced benefit from atezolizumab in this study and the lack of strong biomarker evidence should provoke caution in recommending this treatment to patients with TNBC, for whom, she said, other advanced treatments may be available.

Schmid responded that caution in treatment selection still is advisable when it comes to atezolizumab, but he added that approved advanced treatments for TNBC are lacking and that chemotherapy remains the standard for TNBC, which accounts for 10% to 20% of all patients with breast cancer.

“The fact that we have a small group that benefits and have had such a substantial benefit in terms of long duration of response and also a long survival—that gives me hope. But it’s obviously not a solution for all patients, and we can’t say that every patient should have a single agent immune checkpoint inhibitor, because the response rates at the moment are too low. To me, this is the start of immunotherapy in TNBC, and our goal has to be to improve the number of patients who respond to these therapies.”

The study was described as the largest of its kind so far in TNBC. Although there have been studies of other checkpoint blocking drugs in TNBC over the last few years, also showing response rates, this week’s report on atezolizumab was the first on OS in this patient population, presenters said.

In the study, while all responders were alive after 1 year, the 1-year survival rate for nonresponders was only 38%. TNBC patients treated with atezolizumab had a prolonged median duration response of 21 months, which Schmid said was substantially longer than has been seen with any other treatment for patients with metastatic TNBC.

In the study, 19 patients received atezolizumab as first-line treatment, whereas 93 had received at least 2 lines of prior therapy. Patients could be divided into 2 categories: those with PD-L1 expression on <5% of immune cells (ICs) and those with PD-L1 expression on &ge;5% of ICs. Of the RECIST v1.1 responders, 5 received atezolizumab as first-line therapy and 9 had disease with high PD-L1 expression (IC2/3).

One- and 2-year OS for patients who received atezolizumab as initial first-line treatment was 63% and 47%, respectively. For those who received 2 or more lines of prior therapy, OS rates were 37% and 18%, respectively.

One-year OS for patients with high PD-L1 expression (IC2/3) was 45%, versus 37% for those with low-to-no PD-L1 expression (IC0/1).

Atezolizumab is currently approved for metastatic urothelial cancer after chemotherapy and for treatment of patients with metastatic non—small cell lung cancer. Schmid in his conclusions noted that study of atezolizumab in the first-line TNBC setting continues with the randomized phase III study IMpassion130, which is investigating the drug&rsquo;s efficacy in combination with chemotherapy.

Reference:

Schmid P, Cruz C, Braiteh FS, et al. Atezolizumab in metastatic triple-negative breast cancer: long-term clinical outcomes and biomarker analyses. Abstract presented at: AACR Annual Meeting 2017; April 1-5, 2017; Washington DC. Abstract 2986.

&ldquo;Atezolizumab has yielded durable responses in a small population of both previously untreated and pretreated TNBC patients and is associated with an excellent safety profile,&rdquo; he said.