Novel Therapies for HER2+ Breast Cancer and Brain Metastases

Sara A. Hurvitz, MD, and Julia A. LaBarbera, NP, of UCLA, highlight the safety and efficacy profiles of newer novel treatment options available for HER2-positive breast cancer and brain metastases.

Sara A. Hurvitz, MD: The field of breast cancer treatment in the HER2 [human epidermal growth factor receptor 2]–positive realm has rapidly changed. Even in the last year, we’ve seen data that are practice changing. It had been that T-DM1 [trastuzumab emtansine] was the gold standard second-line therapy, based on the AMELIA clinical trial. This is the therapy that Erika received in the second-line setting. But we just saw data from the DESTINY-Breast03 clinical trial looking at T-DXd [trastuzumab deruxtecan], another antibody-drug conjugate, compared with T-DM1 [trastuzumab emtansine]. It was a large phase 3 study that showed T-DXd [trastuzumab deruxtecan] was associated with a substantially improved progression-free survival for patients treated with T-DXd [trastuzumab deruxtecan], with a hazard ratio of 0.28. This makes T-DXd [trastuzumab deruxtecan] the standard second-line option and places T-DM1 [trastuzumab emtansine] in a later position.

As I mentioned, we have tucatinib-capecitabine-trastuzumab in the third-line setting and beyond, but also appropriate in the second-line setting for patients with brain metastases. We have a bunch of other agents as well: lapatinib-based therapy, neratinib-based therapy, trastuzumab combined with other chemotherapy, and now margetuximab. Sequencing of these agents is not entirely clear because we don’t have enough clinical trial data to address that. But the NCCN [National Comprehensive Cancer Network] Guidelines, are an appropriate resource for us to turn to when we’re making decisions about systemic therapy.

Julia, take us through, at a high level, some of the adverse effects we watch for with newer agents, in particular tucatinib and T-DXd [trastuzumab deruxtecan].

Julia LaBarbera, NP: T-DXd [trastuzumab deruxtecan] can cause a lot of nausea, neutropenia, and diarrhea. One of the more serious adverse effects we need to look out for is interstitial lung disease [ILD], or pneumonitis. This could be asymptomatic. It’s something that we need to monitor for on the scans. Then, of course, we educate patients to report any new cough, shortness of breath, or activity intolerance. Tucatinib is fairly well tolerated, though you can experience significant diarrhea and hepatotoxicity. We do need to keep monitoring liver enzymes and stay on top of a patient’s symptoms, encouraging them to report diarrhea that’s not well controlled.

Sara A. Hurvitz, MD: Excellent. Pneumonitis—an inflammation of the lungs—with T-DXd [trastuzumab deruxtecan] can be a serious adverse effect in about 10% of patients. Any patient on T-DXd [trastuzumab deruxtecan] who develops shortness of breath needs to bring it to the clinician’s attention. If any ground-glass opacities are seen on imaging of a patient being treated with T-DXd [trastuzumab deruxtecan], the therapy needs to be held. It’s rare to have death. The DESTINY-Breast03 trial with T-DXd [trastuzumab deruxtecan] didn’t have any deaths due to ILD. With careful attention, this can be mitigated. As you mentioned, with tucatinib, diarrhea is the biggest challenge we’re seeing with our own patients, but it’s fairly easy to manage given the HER2 selectivity of this agent.

Transcript edited for clarity.

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