Women with metastatic triple-negative breast cancer (TNBC) who respond to the anti-PD-L1 immunotherapy Tecentriq (atezolizumab) live significantly longer than those who do not, according to data from a Phase 1 clinical trial.
“Triple-negative breast cancer is an aggressive subtype of breast cancer often affecting younger women and, unfortunately, the current treatment options for metastatic disease remain limited,” Peter Schmid, MD, PhD, director of St. Bartholomew’s Breast Centre and Barts Cancer Institute in London, said in a press release.
According to Schmid, the trial included the largest cohort of metastatic breast cancer patients treated with immunotherapy to date. It is also the first to report the survival outcomes of TNBC patients. Its results were presented in early April at the American Association for Cancer Research 2017 Annual Meeting, in Washington, D.C.
The open-label, dose-escalation Phase 1 trial (NCT01375842) recruited metastatic TNBC patients to one of the expansion cohorts. Among the 112 patients evaluable for response, 93 had received two or more prior lines of therapy, and 19 had received Tecentriq as first-line treatment. To examine whether response rates depended on levels of PD-L1, each patient was assessed at baseline for the presence of this protein on immune cells inside the tumor. Doctors performed the test using an antibody developed by Roche.
Patients fell into one of two categories; those with less than 5 percent of immune cells expressing PD-L1, and those with 5 percent or more of immune cells expressing PD-L1. Results show that 11 patients responded to the treatment, amounting to a overall response rate of 10 percent.
“The most significant finding is the difference in the overall survival between patients who responded to atezolizumab and patients who did not respond. While all responders were alive after one year, the one-year survival rate for nonresponders was only 38 percent,” Schmid said. “Another noteworthy finding is that metastatic TNBC patients treated with atezolizumab had a prolonged median duration of response of 21 months, which is substantially longer than what has been seen with any other treatment to date for this patient population.”
Among the 11 responders, five received Tecentriq as first-line therapy, and nine had high levels of PD-L1 expression, suggesting that women with that characteristic were more likely to respond to Tecentriq. Consistently, stratifying patients based on line of treatment or PD-L1 expression also revealed improved survival rates for those receiving Tecentriq as first line treatment and for those with high PD-L1 expression.
One- and two year overall survival for patients receiving Tecentriq as first-line treatment were 63 percent and 47 percent, respectively. That compared to 37 percent and 18 percent in patients who had received at least one prior line of treatment. Similarly, one-year overall survival was 45 percent for patients with high PD-L1 expression, compared to 37 percent in those with low to no PD-L1 expression.
Only 11 percent of participants experienced Treatment-related grade 3 or 4 side effects, while three patients discontinued treatment due to side effects.
“Atezolizumab has yielded durable responses in a small population of both previously untreated and pre-treated TNBC patients and is associated with an excellent safety profile. The results provide further evidence that immunotherapy may play a significant role in the treatment of breast cancer,” Schmid said. “It will be down to other ongoing and future studies to further improve on these treatment outcomes by optimizing treatment regimens and combinations for this hard-to-treat group of patients.”