ASCO recently updated its guideline on systematic therapy for patients with HER2-positive advanced BC to reflect data that were published between 2016 and 2021. A previous update had been issued in 2018.
An expert panel conducted a systematic review to determine the optimal regimen for advanced HER2-positive BC: either HER2-targeted therapy monotherapy or HER2-targeted therapy combination therapy with chemotherapy and/or endocrine therapy. It made recommendations for first-, second-, and third-line or greater treatment options.
For first-line therapy, the experts reaffirmed their previous recommendation for the use of combination therapy with trastuzumab, pertuzumab, and a taxane, unless a taxane is contraindicated; this was based on high-quality evidence and a strong recommendation.
For second-line therapy, a new recommendation was issued based on moderate-quality evidence but a strong recommendation that if there is disease progression during or after first-line HER2-targeted therapy and trastuzumab deruxtecan has not been used, this latter agent should now be employed. In the 2018 guideline, trastuzumab emtansine had been recommended, but more recent data demonstrated that trastuzumab deruxtecan provided superior progression-free survival (PFS) compared with trastuzumab emtansine. Caution is advised since trastuzumab deruxtecan is associated with severe induced interstitial lung disease and pneumonitis.
For third-line or greater therapy, the choice of therapy should be based on the treatment schedule, routes of administration, and toxicities during the decision-making process since there is insufficient evidence to recommend one regimen over another if the patient’s disease has progressed during or after second-line or greater HER2-targeted therapy and pertuzumab and trastuzumab deruxtecan have already been administered. If pertuzumab has not been utilized, it can be offered (no change from 2018).
New treatment options include the use of trastuzumab emtansine (high-quality evidence, strong recommendation); tucatinib with trastuzumab and capecitabine (moderate-quality evidence, strong recommendation); trastuzumab deruxtecan (moderate-quality evidence, strong recommendation); neratinib with capecitabine (moderate-quality evidence, weak recommendation); margetuximab and chemotherapy (moderate-quality evidence, weak recommendation); and abernaciclib combined with trastuzumab and fulvestrant (moderate-quality evidence, weak recommendation).
No change was made to the recommendation that if a patient has not received pertuzumab previously it may be offered now, but this is a weak recommendation with insufficient quality of evidence. Trastuzumab emtansine should be offered for third-line or further therapy if it was not administered second-line. Tucatinib has demonstrated increased PFS and overall survival as third-line therapy, and it is particularly useful for patients with brain metastases. Capecitabine with neratinib may be superior to capecitabine with lapatinib. Other third-line agents are preferred over margetuximab since its clinical benefit was found to be negligible. Those with the CD16A-158F allele may benefit from margetuximab over trastuzumab; however, the biomarker for this allele is not clinically available. The combination of abemaciclib, trastuzumab, and fulvestrant may be beneficial in patients with hormone receptor–positive disease.
Other recommendations listed in the 2018 guideline and are still mentioned in the new update that have “weak” recommendations but a moderate quality of evidence include the use of lapatinib with trastuzumab, lapatinib with capecitabine, other combinations of chemotherapy and trastuzumab, and the use of hormonal therapy in patients who are either estrogen– and/or progesterone–receptor positive.
Although these were not changes, the guideline restates that in patients with double-positive (estrogen or progesterone receptor and HER2-receptor positive) or triple-positive BC (estrogen, progesterone, and HER2-receptor positive), HER2-targeted therapy with chemotherapy or endocrine therapy plus trastuzumab or lapatinib (when appropriate) or endocrine monotherapy (when appropriate) can be administered. If HER2-targeted therapy in conjugation with chemotherapy has already been initiated, when chemotherapy is completed and/or if there is disease progression, endocrine therapy may be added. Keeping in mind that the guideline does not consider individual variations among patients, these new recommendations provide pharmacists with additional guidance in the management of patients with advanced HER2-positive BC.
The content contained in this article is for informational purposes only. The content is not intended to be a substitute for professional advice. Reliance on any information provided in this article is solely at your own risk.
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