Dr Cortés Discusses First Line Immunotherapy in mTNBC

Hello, my name is Javier Cortes. I am leading the International Breast Cancer Center in both cities in Madrid and Barcelona. We have been discussing the role of immunotherapy in the first-line treatment of metastatic triple-negative breast cancer. Did you know, triple-negative breast cancer is a good target for immunotherapy for different reasons?

It has a high mutation rate compared with other breast cancer types. It also has, at least many of our patients, an important and significant number of T cells in the tumor. Also, it usually express PD-L1. We will know the data we have with different immunotherapeutic agents when used in single agent in the treatment of these patients.

In the late-line setting, the overall response rate is low in the range of maybe 5-7%. It is true that when compared with chemotherapy, it did not prolong survival. It is very difficult to justify the use of immunotherapy in single agent. However, in combination with chemotherapy in the first-line setting, we got very important and interesting data.

We have three randomized phase 3 studies which have been published or presented in important meetings. The IMpassion130, IMpassion131, and KEYNOTE-355. In brief, when atezolizumab has been combined with nab-paclitaxel but not with paclitaxel, it improves progression-free survival in PD-L1 positive patients. However, we have not observed an improvement in overall survival.

In KEYNOTE-355, pembrolizumab was combined with different chemotherapy-based strategies. Pembrolizumab improved progression-free survival with a hazard ratio of about 0.65 in PD-L1 positive patients measured with a CPS score of 10 or more. It is important to know that later this year, we will have definite data for overall survival.

One key aspect of immunotherapy in triple-negative breast cancer is the PD-L1 expression. It is true that improvement in progression-free survival has only been observed in patients with expression of this marker. However, different platforms and different antibodies have to be considered if we want to use atezolizumab or pembrolizumab.

Different antibodies, different platforms, different cutoff values, and different modalities of scoring calculation are important to take into account. In brief, for atezolizumab, the antibody SP142 on VENTANA platform should be used. In contrast, if we are going to use pembrolizumab, we should go for the antibody 22C3 in the Dako platform.

It is very important to remark that these assays are not interchangeable. One important aspect also to take into account in the clinic is the sample that we should measure PD-L1. What is very clear is that usually, in the primary tissue, the positivity of this marker is in the range of 44%

In the metastatic TNBCs, it decreases to 36%. Of interest, it might be more important in some organs such as breast, lymph nodes, or skin compared with others like liver. Last but not least, I want to make a very brief comment about toxicity.

Usually, when immunotherapy is combined with chemotherapy, we do not observe a significant increase in the grade 3 and 4 adverse events. But of course, as unexpected, the toxicities related with the immunotherapy is clearly observed in the immune-based arm.

Indeed, grade 3-5 adverse events, immune-mediated adverse events, are increased up to 5% when immunotherapy is combined with chemotherapy, being the most important ones, hypo and hyperthyroidism.

In conclusion, I think that immunotherapy in combination with chemotherapy is a good approach for patients with PD-L1 positive tumors. It is very important to remark that today, we do not have improvement in overall survival. This is something that hopefully, we will see in the upcoming months.

Last but not least, I would like to highlight two more things. The first one, we should not remember the use of biomarkers. They are not interchangeable. Finally, immune-related adverse events are new adverse events for oncologists, are diverse and uncommon. We have to know them and we have to manage them in an appropriate way. Thank you.