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Atezolizumab prolongs OS for responders with triple-negative breast cancer
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Patients with triple-negative breast cancer who responded to atezolizumab experienced longer OS than patients who did not respond or used other treatments, according to data from a phase 1a clinical trial presented at the American Association for Cancer Research Annual Meeting.
“Atezolizumab [Tecentriq, Genentech] has yielded durable responses in a small population of both previously untreated and pretreated triple-negative breast cancer patients and is associated with an excellent safety profile,” Peter Schmid, MD, PhD, FRCP, professor in the Centre for Experimental Cancer Medicine at Barts Cancer Institute of Queen Mary University London, said in a press release. “The results [of this study] provide further evidence that immunotherapy may play a significant role in the treatment of breast cancer.”
Most patients with triple-negative breast cancer develop resistance to chemotherapy quickly and the median survival remains low, according to Schmid.
“Most patients pretreated with chemotherapy have response rates below 20%, and it was even lower among this group of [study] patients,” Schmid said during a press conference.
Due to poor patient prognosis and lack of treatments, Schmid and colleagues studied the safety and efficacy of atezolizumab— a humanized mAb inhibitor — among an expansion cohort of patients with triple-negative breast cancer, regardless of PD-L1 status.
Patients received either 15 mg/kg, 20 mg/kg or 1,200 mg of atezolizumab intravenously for 1 year with the option for retreatment if disease progressed or if clinical benefit ended. Nineteen patients received atezolizumab as first-line therapy and 93 received at least two prior lines of therapy.
Eleven patients responded to treatment, which included complete and partial responses, for an overall response rate of 10%. Five of these patients received atezolizumab as first-line treatment and nine had high PD-L1 expression.
Median OS was 9.3 months over a follow-up of 50 months.
OS rates at 1 and 2 years were 100% for responders compared with 33% at 1 year and 11% at 2 years in nonresponders. Rates of OS were greater among patients who received atezolizumab as first-line therapy than patients who received it as second-line therapy at 1 year (63% vs. 37%) and 2 years (47% vs. 18%).
One-year OS was 45% for patients with high PD-L1 expression compared with 37% among patients with low or no PD-L1 expression.
“The most significant finding is the difference in the OS between patients who responded to atezolizumab and patients who did not respond,” Schmid said, adding that patients treated with atezolizumab had a prolonged median duration of response of 21 months.
Atezolizumab appeared generally well tolerated. Eleven percent of patients experienced grade 3 and grade 4 adverse events and 3% of patients discontinued treatment due to side effects.
Because no randomized control group existed that received standard therapy, the survival data could be seen only in the context of historical controls, which limited the study findings.
This is the first study to report on OS results in patients treated with atezolizumab, according to Suzanne L. Topalian, MD, director of the melanoma program and associate director of Bloomberg-Kimmel Institute for Cancer Immunotherapy at Johns Hopkins Medicine.
“This study is the largest of its kind. Although there have been reports with other checkpoints also showing response rate, today we heard the first overall survival [rates] in these patients,” Topalian, who was not involved with the study, said during the press conference. “As Dr. Schmid pointed out, there is evidence of ongoing immune response in these patients ... Therefore, this is a likely target to bring forward for trials.” – by Melinda Stevens
Reference:
Schmid P, et al. Abstract 2986. Presented at: American Association for Cancer Research Annual Meeting; April 1-5, 2017; Washington, D.C.
Disclosures: The study was funded by Genentech. Schmid reports his spouse is a consultant for Roche/Genentech. Topalian reports research grants from Bristol-Myers Squibb.
Perspective
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Paula Klein, MD
It is terrific to see such exciting data on triple-negative breast cancer, which occurs in 15% of all breast cancers. Triple-negative breast cancer is devoid of targets such as ER, PR receptor and the HER-2 neu receptor which limits its therapeutic options.
Breast cancer has been a bit slow to the immunotherapy party enjoyed by other solid tumors. The triple-negative subset is rich in immune cells and presents the strongest immunogenic potential. Thus, it is ripe for the first entry into the immunotherapy field.
This study demonstrates the enormous potential of immunotherapy specifically atezolizumab (Tecentriq, Genentech) to prolong survival in patients with triple-negative breast cancer and improve outcomes. This phase 1 study evaluated 122 patients who received atezolizumab as first-line treatment or who had received up to two prior lines for advanced disease. It included those who had PD-L1 expression on less than 5% of immune cells or 5% or more of immune cells.
The overall response rate to first-line treatment, as expected, was higher than second or third line. Also, tumors with higher PD-L1 expression had a higher response. It is the duration of response that is most notable nearly 2 years. It is important to note that no concurrent chemotherapy was given.
These outcomes surpass any of our usual results with chemotherapy options in triple-negative breast cancer in the advanced setting. Immune infiltrates, such as TILs and CD8, have been described as predicting superior outcomes in both triple-negative breast cancer and HER-2positive subsets. This study also confirms this finding. We look forward to many more studies of immunotherapy in breast cancer and expect exciting breakthroughs in all stages of breast cancer, particularly triple-negative breast cancer and likely HER-2positive breast cancer.
Perspective
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Amy Clark, MD, MSCE
This study examined atezolizumab (Tecentriq, Genentech) in 112 patients with triple-negative breast cancer in a phase 1a trial. The majority of patients had received one or two lines of chemotherapy. A small minority of patients did experience a response to the drug, and those who responded lived significantly longer than those who did not respond.
This highlights the fact that immunotherapy will be effective for some triple-negative breast cancers. These preliminary, but promising, results may lead to improved outcomes for some patients with metastatic triple-negative breast cancer.
The critical issue will be our ability to identify the subset of patients who will benefit. The biomarkers examined in this trial did not predict who would respond to the drug.
Additional studies comparing atezolizumab to standard therapy and examining additional novel predictive biomarkers will be helpful in understanding the exact benefit of the drug and in whom it works.
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