As part of our coverage of the 2017 American Association for Cancer Research (AACR) Annual Meeting, held April 1–5 in Washington, DC, we are speaking today with Peter Schmid, MD, a medical oncologist and director of the breast cancer center at the Barts Cancer Institute in London. At the AACR meeting, Dr. Schmid presented long-term data on the anti–programmed death ligand-1 (anti–PD-L1) immunotherapy atezolizumab in metastatic triple-negative breast cancer.
—Interviewed by Anna Azvolinsky
Cancer Network: As background, can you tell us about the rationale for targeting triple-negative breast cancer with an anti-PD-L1 antibody?
Dr. Schmid: Triple-negative breast cancer is a subtype of breast cancer probably with the highest need at the moment. Unfortunately, the median survival of patients with metastatic triple-negative breast cancer is still in the range of 9–12 months, and there is an urgent need for targeted therapies. Triple-negative breast cancer is associated with a higher rate of mutations, and therefore a higher rate of neo-antigens. It also has more frequent tumor-infiltrating lymphocytes than other breast cancer subtypes, which are more prognostic in triple-negative disease than in other subtypes. These are all conditions that suggest that cancer immunotherapy could play a significant role in triple-negative breast cancer and that was partly the basis and rationale for setting up this expansion cohort for patients with metastatic triple-negative breast cancer.
Cancer Network: Can you talk about the particular design of the study and the specific expansion cohort on which you presented data?
Dr. Schmid: The data we presented were on 115 patients with metastatic triple-negative breast cancer who were treated within a large, non-randomized phase I study with single-agent atezolizumab. This is an expansion cohort that included patients mainly with pre-treated metastatic disease, but also a smaller group of patients who had not received prior chemotherapy for their metastatic breast cancer. All patients were required to have measurable breast cancer with metastatic lesions.
Cancer Network: What were the main efficacy findings?
Dr. Schmid: There were three significant findings in my opinion. The first finding was that we see a clear difference in response to single-agent atezolizumab with regard to the line of therapy. Whereas patients who received atezolizumab as first-line therapy had a response rate of 26%, the response rate in pre-treated patients was 7%.
The second finding was a substantially longer duration of response than what we frequently see with other treatments—although this is obviously a non-randomized study. The median duration of response to atezolizumab was 21 months, which in my opinion, is an important result.
The third finding was with regards to survival. When we assessed patients who responded to atezolizumab and compared them to patients who did not have a treatment benefit from atezolizumab, there was a clear difference in outcomes. Unfortunately, all patients who did not respond to atezolizumab passed away in the first 2 years, with a 1-year survival rate of 38%. All patients who responded to atezolizumab were still alive after 2 year’s time.
Cancer Network: Did you and your colleagues look at PD-L1 tumor expression or any other biomarkers that may predict response, particularly as triple-negative breast cancer patients can be a heterogeneous population of patients.
Dr. Schmid: So this study did assess the link between PD-L1 expression and outcome and also looked into other biomarkers for treatment, as well as changes in biomarkers while on treatment. There is a weak and non-significant correlation between PD-L1 expression and response. If you look at immune-related response, then the response in patients with high PD-L1 expression was 70% compared to 8% in PD-L1–low or PD-L1–negative patients. But again, PD-L1 taken on its own does not seem to be a good biomarker for selecting patients for these treatments. We will probably require a more composite set of biomarkers incorporating different features and some of this work is still ongoing.
Cancer Network: Just lastly, what is the follow-up plan for this study? Are there other studies that are starting soon or are being planned?
Dr. Schmid: There is a large program that is ongoing with immune checkpoint inhibitors in triple-negative breast cancer and also a large program with atezolizumab as one of the immune checkpoint inhibitors. Most of the efforts at the moment are focusing on combinations of chemotherapy and immune checkpoint inhibitors. There is probably only a small group of patients who will benefit from single-agent checkpoint inhibition. In our trial overall we had only 15 patients who responded out of more than 100 patients—so a relatively small group will respond to single-agent therapy. The focus going forward will be on combination studies. There are randomized studies ongoing and near completion in terms of recruitment—for example, paclitaxel with or without atezolizumab in first-line metastatic triple-negative breast cancer—that will hopefully give us some answers on the role of immune checkpoint inhibitors in triple-negative breast cancer in the near future.
Cancer Network: Thank you so much for joining us today, Dr. Schmid.
Dr. Schmid: My pleasure. Thank you very much.