Abstract
The anti–PD-L1 drug atezolizumab produced durable responses among 10% of patients with triple-negative breast cancer in a large phase I trial presented at the American Association for Cancer Research Annual Meeting 2017. The therapy proved safe, with the highest response rates seen in women who received the drug as a first-line therapy and in those with elevated PD-L1 levels and other tumor biomarkers.
Immunotherapy might not work for many patients with metastatic triple-negative breast cancer (TNBC), but those who do respond achieve lasting remission.
That's the finding of a phase I study of 112 women with metastatic TNBC treated with atezolizumab (Tecentriq; Roche)—the largest cohort of evaluable patients with TNBC receiving immunotherapy reported to date. Overall, only 10% responded to the anti–PD-L1 therapy, but among those who did, the median duration of response was 21 months—the longest ever seen with any treatment for TNBC. In addition, all of those who responded were still alive 2 years after starting therapy.
By comparison, the 2-year survival rate for nonresponders was just 11%. This percentage is likely inflated because 4 patients with pseudoprogression were counted as nonresponders. These patients would have been classified as responders if the investigators had relied on immune-related evaluation criteria instead of standard RECIST 1.1.
Importantly, the therapy proved safe, with only 11% of trial participants experiencing serious side effects.
“This is the start of immune therapy in triple-negative breast cancer,” said Peter Schmid, MD, PhD, from St. Bartholomew's Hospital and Barts Cancer Institute in London, UK, who presented the results on April 3 at the American Association for Cancer Research Annual Meeting 2017 in Washington, DC. “The fact that we have a group that benefits from single-agent immune therapy and has such a substantial benefit in terms of long duration of response and also a long survival time—that gives me hope, but it's not a solution for all patients.”
Schmid and his colleagues also performed subgroup analyses and found a number of noteworthy trends. The overall response rate (ORR) to atezolizumab was higher among women who received the drug as a first-line therapy compared with those who were previously treated with chemotherapeutic agents or anti-VEGF therapy (26% versus 7%). Also, women with elevated PD-L1 levels on their tumor-infiltrating immune cells posted a higher ORR compared with women with no or low PD-L1 expression (13% versus 5%).
The researchers additionally measured the levels of tumor-infiltrating lymphocytes and CD8+ T cells in tumor biopsies and found that increased expression of these immune markers was associated with a trend toward higher ORRs and longer survival times. “But all these markers weren't black and white in a way that we could say, ‘We can select all the responders based on this, or can deselect a certain group,’” Schmid said.
“What we need to focus on moving forward is to try to improve the response rates with combination therapies and also work to identify biomarkers that help predict response to treatment,” said Rita Nanda, MD, a co-investigator on the atezolizumab study from the University of Chicago Medical Center in Illinois, and the lead researcher of a phase I trial of the PD-1 inhibitor pembrolizumab (Keytruda; Merck) in women with TNBC who had PD-L1–positive tumors. In that study, which Nanda originally published last May in the Journal of Clinical Oncology with follow-up data presented at the December 2016 San Antonio Breast Cancer Symposium, pembrolizumab produced complete or partial responses in 18.5% of the 27 evaluable participants, with long-lasting benefits experienced by three of the five responders.
Pembrolizumab and atezolizumab are each currently in phase III trials for advanced TNBC. Pembrolizumab is being tested as a monotherapy in two studies and in combination with five different chemotherapies—including anthracyclines, alkylating agents, and a taxane—in another. Roche's only phase III trial involves administering atezolizumab alongside the next-generation taxane nab-paclitaxel (Abraxane; Celgene). –Elie Dolgin
