Expert oncologist Virginia Kaklamani, MD, DSc, shares her perspectives on a patient case of HER2+ metastatic breast cancer (mBC) treated with multiple lines of therapy.
Virginia Kaklamani, MD, DSc: Hello, and welcome to this OncLive® My Treatment Approach program titled “Improving Outcomes in Metastatic HER2+ Breast Cancer: Translating Evidence to Clinical Practice.” I’m Virginia Kaklamani, a professor of medicine at UT [University of Texas] Health [Science Center] at San Antonio MD Anderson Cancer Center, in San Antonio, Texas. I’m going to discuss recent advances in the treatment of metastatic HER2 [human epidermal growth factor receptor 2]–positive breast cancer and its impact on clinical practice. I’ll present the hypothetical patient case and discuss my treatment approach to illustrate how we incorporate recent data in our practice. Let’s get started.
This patient initially presented with right breast pain. She is 63-years-old and postmenopausal and has a past medical history of hypertension, COPD [chronic obstructive pulmonary disorder], and anxiety disorder. She presented post-mammogram with a right upper outer quadrant lesion. This was confirmed on ultrasound, and she had a biopsy that was positive for infiltrating ductal carcinoma, HER2+ and IHC3+ [immunohistochemistry], and ER [estrogen receptor] and PR [progesterone receptor] negative. In her review of systems, she reports that she had a weight loss of 30 lb in the past 4 months, a decrease in appetite, and fatigue exertional dyspnea. Because of that, she has an ECOG performance status of 1.
Her past medical history included hypertension, hyperlipidemia, COPD, and anxiety disorder. Her family history includes a mother with colon cancer and a father with a myocardial infarction. On physical exam, she is anxious. She has a breast exam that shows a right upper-outer quadrant mass, at the 11 o’clock position, around 5 cm in size. It’s tender to the touch. On deep palpation it’s immobile, but there’s no erythema or discharge and no lymphadenopathy has appreciated. On imaging, her mammogram reveals a 4.5-cm mass. She has CT scans that show multiple metastases to the liver, lungs, and bones, and she has an MRI of the brain that’s negative for metastatic disease.
In April 2018, she has a biopsy that shows HER2+, ER/PR-negative breast cancer. She also has a liver biopsy confirming the same findings. In May of the same year, she starts treatment with docetaxel, trastuzumab, and pertuzumab as the initial therapy; this is the CLEOPATRA regimen. She is found to have progression of disease in February 2019, so the response and stable disease lasted for a little less than a year. At that point, she’s switched to trastuzumab deruxtecan. But 3 months later, she’s found to have interstitial lung disease [ILD]. What we do next? What will our third-line option be? There are several options to consider, including T-DM1 [trastuzumab emtansine] and the combination of tucatinib, trastuzumab, and capecitabine therapy. Ultimately, the decision was made to give her T-DM1 [trastuzumab emtansine] and to continue the treatment with T-DM1 [trastuzumab emtansine].
This is a patient going into third-line therapy for metastatic breast cancer. She has received THP [docetaxel, trastuzumab, pertuzumab], which is our standard first-line regimen. Then she’s given T-DXd [trastuzumab deruxtecan], which is our standard second-line regimen based on the DESTINY-Breast03 data. We’re left asking what to do next, especially considering she has developed ILD on T-DXd [trastuzumab deruxtecan]. One consideration is what other agents can potentially cause ILD. T-DM1 [trastuzumab emtansine] is 1 of those agents. There is ILD described with T-DM1 [trastuzumab emtansine]. I’ve had a couple of patients with ILD, so I’d be careful with giving T-DM1 [trastuzumab emtansine] right after a diagnosis of ILD. I’d favor giving tucatinib to this patient. As we know from clinical trial data, tucatinib is effective regardless of the presence or absence of brain metastases. The HER2CLIMB trial showed a good benefit and an improvement in overall survival in patients in the overall patient population. I don’t necessarily label tucatinib as the brain metastases drug. I label it as my third-line regimen for HER2+ metastatic breast cancer.
Transcript edited for clarity.