Charles Powell, MD, MBA, director of the Mount Sinai-National Jewish Health Respiratory Institute, discusses the questions surrounding pulmonary toxicities when using anti-HER2 antibody-drug conjugates (ADCs) such as trastuzumab deruxtecan (Enhertu) for patients with HER2-positive metastatic breast cancer.
The main question regarding anti-HER2 ADCs is why they cause pulmonary adverse events such as interstitial lung disease. The premise and promise of drugs like trastuzumab deruxtecan is that there is more targeted delivery of the anti-neoplastic agent to the cancer cells of interest, according to Powell. But the proteins that are being targeted are rarely expressed only on the tumor cells and not on other cells in the body. He says this concept is true with the HER2 protein when it is targeted by trastuzumab deruxtecan, as well as other antibodies being used in this targeted strategy.
Another important question is why this toxicity is seen in some patients with HER2-positive breast cancer but not in others? Powell says the overall incidence of these toxicities is about 15.5% to 15.8%, which means there are a vast majority of patients who do not develop pulmonary toxicity even though they are receiving the same drug at the same dose for the same disease of HER2-positive metastatic breast cancer. Investigators are looking into what makes an individual likely to develop pneumonitis or other pulmonary toxicities compared with other patients.