Around the Practice: Updates in Treating HER2+ Breast Cancer - Episode 8

Patient Case 2: 56-Year-Old Woman Presented With New Right Breast Mass

Patient Case 2 is presented, and Dr Gadi and Dr Mahtani detail how they would proceed with treating this patient.

Sara Hurvitz, MD:Let’s move on to Patient Case 2. This is a 56-year-old woman who presented with a new right breast mass diagnosed on screening mammogram. An MRI of the breast showed the 2.5-cm mass in the right breast but also axillary lymph nodes. The biopsies were done. It was ER [estrogen receptor]/PR [progesterone receptor] negative, HER2 [human epidermal growth factor receptor 2]–positive invasive ductal carcinoma. Scans were negative for metastases, she doesn’t have any cardiovascular disease or family history of cancer. She has 1 child, and she had menopause at age 51. She completed 6 cycles of neoadjuvant TCHP [docetaxel, carboplatin, trastuzumab, pertuzumab] with a nice response to therapy. She underwent a right mastectomy and an axillary lymph node dissection. She had 0.8 cm of residual disease, received adjuvant T-DM1 [trastuzumab emtansine] according to the KATHERINE study, and completed 9 of 14 cycles, but she stopped early because of neuropathy. Six months after stopping adjuvant T-DM1 [trastuzumab emtansine], she had a recurrence in the liver; biopsy confirmed that it’s HER2+ metastatic breast cancer. A brain MRI was also done, and she was positive for 2 brain metastases. The largest was 2.1 cm in the right frontal lobe, assuming she had some symptoms to prompt the MRI of the brain.

Which therapy would you offer this patient at this point: A) restart T-DM1 [trastuzumab emtansine]; B) tucatinib, trastuzumab, capecitabine; C) T-DXd [trastuzumab deruxtecan]; or D) neratinib? For the purpose of this question, if you’re choosing a therapy, you can assume you’re offering whatever standard locoregional therapy you’d like. This question addresses systemic therapy choices and what you would do from a systemic perspective. She has liver and brain metastases. The winner is going to be tucatinib, trastuzumab, capecitabine, which could be done with or without prior SRS [stereotactic radiosurgery]. In this setting, in the HER2CLIMB study, a patient with a 2.1-cm brain tumor may have been allowed, with approval of the monitor. We have data regarding that situation. V.K., what’s your answer? Seventy percent are choosing tucatinib, and we have about 20% to 25% with T-DXd [trastuzumab deruxtecan]. Any thoughts?

Vijayakrishna Gadi, MD, PhD:I agree with the community choice of a tucatinib-based regimen, for many reasons. This is the type of patient who was enrolled in this study and the survival data that we look at speaks to this patient. More worrisome is the rate of progression. In the first-line setting, brain metastases is very concerning. Patients like this continue to have more evidence of metastases in the CNS [central nervous system] over time. Even if you target these 1 or 2 lesions with stereotactic radiosurgery and pick the tucatinib regimen, you might have an opportunity to suppress future metastases in a patient like this. The other option is a very active regimen with deruxtecan. We now have a hint of data of the CNS being this way. That’s not the patient where we have randomized control data that suggest that is a superior agent to the tucatinib agent. Sticking with the data, I’d go with that, and see what’s going on over time.

Sara Hurvitz, MD:Reshma, what about SRS? Would you use SRS in a patient like this and then follow it with tucatinib-based therapy? Would you use SRS and do T-DXd [trastuzumab deruxtecan]? Or would you do tucatinib and put off locoregional therapy for the time being?

Reshma Mahtani, DO:There’s a saying, “To a carpenter, everyone looks like a nail.” When you send patients to a radiation oncologist, it’s difficult to get them to not offer SRS. Patients who participate on trials are highly selected, and the strategy that was employed in HER2CLIMB would have allowed a patient with a brain lesion that was 2 cm or less and didn’t require immediate local therapy, to be treated with just tucatinib. If it was up to me, I’d like to use just tucatinib knowing that some of these local therapies are associated with other adverse effects. Practical issues arise, like how long does it take you to get the drug into the hands of the patient? Now you have a patient that has a brain lesion, and you’re not treating it with SRS. Most of these patients will be treated with local therapy. This scenario in this case is something that we’ll see more frequently. Because if you look at the KATHERINE data, if you look at high-risk patients who had residual disease, even using our best drug in that setting, T-DM1, it didn’t affect the incidence of brain metastases for those patients. There are ongoing trials looking at that patient with high-risk residual disease. Tucatinib plus T-DM1 [trastuzumab emtansine] in the COMPASS trial looks to see if we can; prevention is the best medicine.

Sara Hurvitz, MD:Neil, are you doing scans for brain metastases in asymptomatic patients if they have HER2+ metastatic disease? Are you scanning those who have symptoms? Once brain metastases have been diagnosed, how often are you scanning the brain to follow them?

Neil Iyengar, MD:Once we have a patient with established brain metastases, I follow them as I would their systemic disease; it’s important for assessing response to their systemic therapy. If we’re using systemic therapies with CNS penetration, then we’re looking for effect in the CNS as well. I’m aiming for systemic imaging every 3 to 4 months, which is something I’m mirroring with the CNS imaging in patients with known or established brain metastases. The first part of your question is more challenging, which is screening for brain metastases. My position on this has evolved over the past few months, from a staunch position of screening only in patients who are symptomatic, but that came from a place where we didn’t have great systemic therapies for our patients with brain metastases. Now that we do, that’s why I’ve changed my opinion. If we’re establishing the diagnosis of metastatic disease, it’s reasonable to screen for brain metastases at that time, up to 50%. In some reports, patients with HER2+ metastatic breast cancer develop brain metastases by the second line of therapy. At the establishment of metastatic disease, and at disease progression, I’ve began screening patients for brain metastases because that might inform my next line of therapy.

This transcript has been edited for clarity.