Trastuzumab Deruxtecan for HER2-Mutant Non-Small Cell Lung Cancer

Pasi Jänne, MD, Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, MA, discusses the recent FDA approval of trastuzumab deruxtecan, a HER2-directed antibody drug conjugate for the treatment of HER2-mutant non-small cell lung cancer. This approval was based on results from the phase 2 trials, DESTINY-Lung01 and DESTINY-Lung02, which demonstrated improved response rate and progress-free survival for patients with non-small cell lung cancer treated with trastuzumab deruxtecan.

Trastuzumab deruxtecan was approved by the FDA on August 11, 2022 for the treatment of patients with unresectable or metastatic non-small cell lung cancer whose tumors have activating HER2 mutations and who have received prior systemic therapy.

Transcript:

Dr Jänne: I'm Pasi Jänne from the Dana-Farber Cancer Institute in Boston, Massachusetts. I'm a medical oncologist with a specialization in thoracic oncology.

What is trastuzumab deruxtecan?

Dr Jänne: Trastuzumab deruxtecan is an antibody drug conjugate where the antibody is targeted against HER2 protein, and it's conjugated to a cytotoxic type of chemotherapy, an extecan derivative, and it's used as an intravenous medication to treat patients with cancer.

What data led to this approval in this population?

Dr Jänne: The data really comes from a clinical trial, the DESTINY-Lung01 trial, whereby patients with HER2-mutant lung cancer were treated with trastuzumab deruxtecan after having failed standard of care, which was chemotherapy, plus or minus immune checkpoint inhibition, and had significant response rate and progression-free survival. And then there's a second trial, that will be presented at the 2022 ESMO Congress, DESTINY-Lung02, that evaluated 2 different doses of the drug that also showed it to have a clinical activity. Those trial results combined with the unmet medical need led to the regulatory approval.

What is the current treatment landscape for patients with this metastatic HER2-low breast cancer?

Dr Jänne: For HER2-mutant lung cancer, current treatment is chemotherapy plus or minus immune checkpoint inhibition. In lung cancer, we have many subsets of the disease where we have specific targeted therapies approved for patients with unique genetic alterations in their cancer.Until now, we have not one had for HER2-mutant lung cancer. Trastuzumab deruxtecan is the first approved targeted therapy for HER2-mutant lung cancer and we're very excited about this and the ability to be able to offer this to our patients

How does trastuzumab deruxtecan fit into the current treatment paradigm?

Dr Jänne: At the moment, it will be used after first-line therapy, so it'll be used as a second-line therapy, but there are additional trials underway evaluating trastuzumab deruxtecan in earlier lines of treatment, and even as first line therapy for someone with HER2-mutant lung cancer.

What is the safety profile of trastuzumab deruxtecan?

Dr Jänne: There are a couple of side effects that have been noted with trastuzumab deruxtecan. First of all, because it's conjugated to a type of a chemotherapy medication, there are some side effects similar to those with chemotherapy — things like nausea and some bone marrow toxicities. The other side effect that has been noted, which can be significant, is interstitial lung disease, essentially an inflammatory process in the lungs that's related to the drug, which can be a safety concern.

Do you think this approval will have an immediate impact in real-world practice?

Dr Jänne: Absolutely, we're already using it. It was already in the NCCN guidelines before this in the United States, but now with the regulatory approval, the use will be even greater. As I said, it's a population of patients where we have not had a targeted therapy prior to this and we're excited about being able to offer this for our patients.

What advice do you have for practicing oncologists that are interested in using trastuzumab deruxtecan for their patients with HER2-mutant non-small cell lung cancer?

Dr Jänne: First of all, you have to know which of your patients has a HER2-mutant lung cancer. The first part is, test your patients. Test them for all the known genetic alterations, including HER2 mutations, where we now have approved targeted therapies for lung cancer. And if you find a patient with one of these alterations, then consider using this as a medication during their treatment journey. As I said, at the current time, it is typically used in the second line setting after having used first line chemotherapy.

What are next steps for investigating trastuzumab in this population or other breast cancer populations?

Dr Jänne: I think next steps for trastuzumab deruxtecan are ongoing trials evaluating in the earlier, so not a second line therapy, but as first line therapy and there are ongoing clinical trials. That of course, then it opens up the possibility of evaluating it in earlier lines of therapy. After surgery, or even before surgery for HER2-mutant lung cancer, and ultimately in combination with other therapies that are used commonly in lung cancer, such as immune checkpoint inhibitors. All of those, I think, are in the queue to be done.