Tecentriq Shows Long-Term Survival in Triple-Negative Breast Cancer


Tecentriq showed impressive long-term survival in patients with metastatic TNBC, according to the results from a recent study.

While researchers are not completely sure of why the drug is so effective for this group, 10 percent of patients with metastatic triple-negative breast cancer (mTNBC) saw impressive long-term survival with single agent Tecentriq (atezolizumab) in a phase 1 study.

Results of the study were presented this week at the AACR Annual Meeting 2017 by lead author Peter Schmid, M.D., Ph.D., 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 one- and two-year overall survival (OS) rates for these responders were 100 percent; for nonresponders, OS rates were 33 percent and 11 percent respectively. Treatment-related grade 3 or 4 adverse events (AEs) were reported for 11 percent of patients, and AEs contributed to discontinuation of treatment in 3 percent of cases, Schmid said.

“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,” he 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, M.D., an oncology contributor for Forbes Magazine, who stated that the small subset of patients who experienced benefit from Tecentriq 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 Tecentriq, but he added that approved advanced treatments for TNBC are lacking and that chemotherapy remains the standard for TNBC, which accounts for 10 percent to 20 percent 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 Tecentriq was the first on OS in this patient population, presenters said.

In the study, while all responders were alive after one year, the one-year survival rate for nonresponders was only 38 percent. TNBC patients treated with Tecentriq 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 Tecentriq as first-line treatment, whereas 93 had received at least two lines of prior therapy. Patients could be divided into two categories: those with PD-L1 expression on less than 5 percent of immune cells (ICs) and those with PD-L1 expression on 5 percent or more of ICs. Of the RECIST v1.1 responders, five received Tecentriq as first-line therapy and nine had disease with high PD-L1 expression (IC2/3).

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

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

Tecentriq 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 Tecentriq in the first-line TNBC setting continues with the randomized phase 3 study IMpassion130, which is investigating the drug’s efficacy in combination with chemotherapy.

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