Expert Discusses Promise of Immunotherapy in TNBC

Giuseppe Curigliano, MD, PhD

The combination of immunotherapy and chemotherapy is showing promising response rates in certain patients with triple-negative breast cancer (TNBC), said ESO Umberto Veronesi Memorial Award Winner Giuseppe Curigliano, MD, PhD, who addressed genetic determinants of breast cancer immunogenicity in his award lecture at the 15th St. Gallen International Breast Cancer Conference.

Curigliano emphasized the importance of patient selection in optimizing immunotherapy in breast cancer. In a study done by Curigliano, in collaboration with the Sidra Medical Center in Qatar, a subgroup of patients with TNBC who would derive benefit from checkpoint inhibitors were identified. This group, he stated, should be selected based on individual assessment of tumor-infiltrating lymphocytes.

Currently, the IMpassion130 trial (NCT02425891) is evaluating the combination of atezolizumab (Tecentriq) and nab-paclitaxel as a first-line treatment for patients with previously untreated metastatic TNBC. In this study, patients are randomized 1:1 to receive either atezolizumab plus nab-paclitaxel or nab-paclitaxel plus a placebo. The primary outcome measures of this ongoing phase III multicenter randomized study are progression-free survival and overall survival.

OncLive: What is the current status of immunotherapy in breast cancer

In an interview with OncLive at this year’s conference, Curigliano, head of the Division of Early Drug Development at European Institute of Oncology, in Milan, Italy, discussed recent trials of immunotherapy and chemotherapy in TNBC, as well as the future role of immunotherapy in the treatment of breast cancer.Curigliano: Many trials are ongoing, and it seems that the combination of immune checkpoint inhibitors plus chemotherapy should be the most promising treatment approach. What we know from the available data is that, as monotherapy, the response rate with an immune checkpoint like pembrolizumab (Keytruda) is about 18% to 20% in TNBC with poor prognosis. If you combine atezolizumab with a chemotherapy like nab-paclitaxel, for example, you may increase the response rate to 40% to 45%—so it is a promising new approach.

The idea behind the combination of immune checkpoints and chemotherapy is that if you treat a patient with chemotherapy, you will induce an immunogenic cell death and then you will be able to boost the immune system with the immune checkpoint inhibitors. I believe that not all patients with TNBC will respond to immune checkpoints, though.

Are there any promising ongoing trials in this area?

The assessment of specific genes will confer much more immuno-reactivity to those tumors, the most pressing challenge is to demonstrate that this combination works.The ongoing IMpassion130 trial is a prospective randomized trial comparing nab-paclitaxel alone versus nab-paclitaxel plus atezolizumab. If these results are positive, it will boost immunotherapy in the field.

Do you foresee immunotherapy having similar success in breast cancer as it has in lung or bladder cancer?

So, major areas of development in metastatic breast cancer are the combinations with chemotherapy in the neoadjuvant setting and that single trial in the adjuvant setting.I think that the selection of the patient will allow us to achieve much more. The key point is to not treat all the patients with immunotherapy, but to focus on improving selection. So, I don't believe we'll replicate the success of lung cancer, bladder cancer, or melanoma here in breast cancer, but if we better select the patients, we will get much more positive results.

Is there anything else you'd like to add?

We have some evidence from clinical trials and from retrospective analysis that patients with higher amounts of tumor-infiltrating lymphocytes are most likely the patients to be candidates for treatment with an immune checkpoint inhibitors. We also have evidence that tumors with a higher mutational load, higher expression of neoantigens, and specific gene signatures are more likely to respond to an immune checkpoint. What I believe is that we need to invest much more in the primary prevention. We need to put more effort in bringing immunotherapeutic approach in the setting of primary prevention. It is very simple, you just need to identify specific antigens, and then develop vaccines. We need to do vaccinations in this setting rather than treating them with 5 years of endocrine therapy with all of those side effects.

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Data from the neoadjuvant trials will be very important, as well. In the neoadjuvant trials, you have a surrogate endpoint of pathologic complete response. And, if you may demonstrate that the addition of an immune checkpoint inhibitor will increase pCR, this will be a strong rationale to move from the neoadjuvant to adjuvant setting. There is already a study ongoing in the adjuvant setting that randomized patients with no pCR following neoadjuvant chemotherapy to have observation versus an immune checkpoint inhibitor for 1 year.