Updated ASCO guidelines for patients with HER2‐positive breast cancer

JANUARY 1, 2023 CANCER Content in this section does not reflect any official policy or medical opinion of the American Cancer Society or of the publisher unless otherwise noted. © American Cancer Society, 2023. T he American Society of Clinical Oncology recently published two updated guidelines on issues related to the diagnosis and treatment of patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer. One guideline focuses on systemic therapy for patients with advanced HER2positive disease,1 and the second centers on the management of patients with HER2-positive disease and brain metastases.2 Both guidelines provide new recommendations based on a systematic evaluation of the best evidence to date by a panel of experts. A key new recommendation for systemic therapy for patients with advanced HER2-positive disease is the use of trastuzumab deruxtecan (T-DXd) as a second-line therapy in patients who progress during or after the first-line HER2-targeted therapy and have not received prior T-DXd. The evidence is based on significant and clinically meaningful improvements in PFS found with the drug according to Jeffrey Kirshner, MD, and Jennie Crews, MD, in a companion article to the update.3 “Given the significant improvement in progression-free survival, trend toward improved survival, and manageable side effects of trastuzumab deruxtecan in second-line metastatic HER2-positive breast cancer, this guideline should be adopted as routine care,” wrote Dr Crews in the companion article.3 Dr Kirshner added that it is likely that most insurance companies will cover the drug for second-line use because of its strong efficacy and its current approval as a third-line therapy. For third-line therapy, the guideline recommends offering other HER2-targeted therapy combinations for patients who progress during or after second-line or greater HER2-targeted therapy. Given the lack of head-to-head evidence to recommend one treatment combination over another, the guideline advises clinicians to talk to patients about other relevant issues such as treatment schedules, routes of delivery, and toxicities. For patients with HER2-positive disease and brain metastases, the new guidance provides several treatment-related recommendations, such as using memantine and hippocampal avoidance (when appropriate) during the delivery of wholebrain irradiation and considering HER2CLIMB (trastuzumab, capecitabine, and tucatinib) as a second-line therapy in patients who are not candidates for T-DXd. Rosana Gnanajothy, MD, a breast oncology attending physician and chair of the regional breast cancer tumor board at the Atlanta VA Medical Center, also highlighted some common clinical questions addressed in the guidance: the recommendation to continue systemic therapy without switching when the disease is not progressing at the time of intracranial progression and to delay local therapy for patients with limited asymptomatic metastases of <3 cm without mass effect while monitoring them on systemic therapy.4 Another clinical question addressed in the guidelines is whether to use routine imaging to screen for brain metastases. The guideline found insufficient evidence to recommend for or against routine screening imaging, but clinicians are advised to have a low threshold for use because of the high incidence of brain metastases in patients with advanced HER2-positive breast cancer. “In my own practice, I review the risk of brain metastases with patients as well as the symptoms that would prompt concern,” says Nancy Lin, MD, a coauthor of the guideline, in an interview with MedPage Today. “I have a very low threshold to order brain MRIs [magnetic resonance imaging] in patients with suggestive symptoms—new/different/worse headaches, unexplained nausea, focal neurological signs or symptoms, etc.” She also says that she reimages on a regular basis those patients who lack symptoms but have a known history of brain metastases.5