First-Line Treatment for Metastatic TNBC: Pembrolizumab + Chemotherapy

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Segment Description:Comprehensive insight on use of first-line pembrolizumab plus chemotherapy in patients diagnosed with metastatic TNBC based on results from the KEYNOTE-355 trial.

Aditya Bardia, MD, MPH: For a patient with PD-L1 positive metastatic TNBC, chemotherapy plus immunotherapy is the main state of management. At this time, in 2022 the preferred immunotherapy is pembrolizumab, that's based on the chemo 355 trial. The chemo 355 trial demonstrated that a combination of chemotherapy plus pembrolizumab was associated with an improvement not only in progression free survival, but also overall survival also since we now practice changing study. In terms of the type of chemotherapy that should be utilized, one could use either atrazine, B-taclitaxel or nab-paclitaxel or one could consider the use of a platinum such as carboplatin. In general, we use a chemotherapy agent that a patient has not used before so you're introducing a new chemotherapy agent that the tumor has not seen in combination with pembrolizumab.

In terms of safety, with immunotherapy plus chemotherapy, you can have adverse effects related to the chemotherapy agent. With carboplatin there could be trauma site apnea. With the use of paclitaxel or nab-taclitaxel, besides mild suppression there could be painful neuro therapy. These are chemotherapy adverse effects that usually oncologists are well familiar with. Then with the addition of immunotherapy you also have immune related adverse events. These are specific adverse events that are related to the immunotherapy agent. Essentially, can affect any organ. The common ones include thyroid abnormality, hypothyroidism or even hyperthyroidism. That could be a colitis which usually manifests as diarrhea. Hepatitis, which usually can be detected by looking at liver enzymes in the blood, and rare adverse effects like pneumonitis or impact on the adrenal glands. Or even neuro therapy, aplastic anemia, essentially any organ can be affected. It's important to monitor patients particularly based on blood work to look for liver enzymes, the endocrine functions so if something is detected that could be corrected with appropriate therapy. These are unique adverse effects related to pembrolizumab, the patients should be consoled about these adverse effects and early intervention is critical to prevent these adverse effects from increasing from say grade one to grade 3 or grade 4.

Whenever we talk about any agent we have to talk both about efficacy as well as quality of life. That's what I usually tell my patients, that my goal is to improve survival as well as your quality of life. Maintaining good quality of life. With the combination of chemotherapy pembrolizumab in the pivotal chemo 355 trial that was maintained. Even from a quality of life perspective, this is a good therapy option. It improves survival, both progression free survival and overall survival. This is important when you're discussing this with patients and starting first line therapy with chemotherapy plus pembrolizumab.

It's great to have survival and quality of life data with chemotherapy plus immunotherapy. This is important when this is discussed with patients. In my opinion, first line therapy for PD-LI positive metastatic TNBC should be chemotherapy plus pembrolizumab. In the second line setting when a patient has disease progression, one could consider antibody drug conjugates. Usually, sacituzumabgovitecanis the preferred agent in the second line setting. Some group analysis from the Essent Trial showed that even in PD-L1 positive metastatic TNBC or patients who received prior immunotherapy there was benefit with sacituzumabgovitecanas compared to standard chemotherapy. It should be the second line option. Another option to consider for HER2 low metastatic TNBC is the use of trastuzumab deruxtecan. Again, similar philosophy even in patients who have received immunotherapy, there's no cross resistance. One could use trastuzumab deruxtecan.

Transcript edited for clarity.