medwireNews: ASCO has released updates to its guidelines for systemic therapy and the management of brain metastases in advanced HER2-positive breast cancer as well as for the use of biomarkers to guide systemic therapy in metastatic breast cancer.
All three guideline updates were developed by multidisciplinary expert panels on the basis of a systematic review of the published literature, and are published in the Journal of Clinical Oncology.
Systemic therapy for advanced HER2-positive breast cancer
The systemic therapy clinical practice guideline updates the previous version published in 2018 and draws on 14 studies (13 randomized controlled trials [RCTs], one single-arm study) published between August 2016 and April 2021.
The guideline makes no change to the first-line treatment option of trastuzumab, pertuzumab, plus a taxane, but recommends trastuzumab deruxtecan as a new second-line option and several new options in the third and later line, including regimens with tucatinib, trastuzumab emtansine, margetuximab, and abemaciclib plus trastuzumab and fulvestrant.
“Overall, there is insufficient evidence to recommend one regimen over another, and the best sequencing of anti-HER2 agents in third-line and greater is unknown,” say the guideline authors.
They continue: “The patient and the clinician should discuss differences in treatment schedule, route, toxicities, etc during the decision-making process.”
Management of HER2-positive breast cancer with brain metastases
The brain metastases guideline also updates a previous version from 2018, and the authors note that “[t]hese recommendations supplement existing guidelines that address brain metastases for patients with other types of cancer and the companion recommendations for systemic therapy.”
A total of four studies, reported in five publications between August 2016 and April 2021, form the evidentiary base for the recommendations, which cover local therapies, such as surgery, whole-brain radiotherapy, and stereotactic radiosurgery, as well as systemic therapy.
The authors outline treatment options by prognosis and number and nature of metastases, ranging from patients with a favorable prognosis and a single brain metastasis to those with poor prognosis and progressive intracranial metastasis despite initial radiotherapy.
The also stress that “clinicians should have a low threshold for magnetic resonance imaging of the brain because of the high incidence of brain metastases” in this patient population.
Biomarkers for systemic therapy in metastatic breast cancer
The final update focuses on the use of biomarkers to help with systemic therapy decisions in metastatic breast cancer, and addresses “topics that have emerged since the publication of the 2015 guideline.”
The new topics range from testing for somatic PIK3CA and ESR1 variants and germline BRCA1, BRCA2, and PALB2 variants to guide targeted therapy to evaluating PD-L1 expression in tumor and immune cells, tumor mutational burden (TMB), and deficient mismatch repair/microsatellite instability to aid immunotherapy decisions.
The recommendations are based on 19 studies published during January 2015–January 2022, mostly phase 3 RCTs or retrospective analyses of biologic samples from patients enrolled in RCTs. But the expert panel highlights that recommendations for certain topics – such as the assessment of TMB – “are based on Panel informal consensus in the absence of studies designed to evaluate the clinical utility of the markers specifically for treatment of [metastatic breast cancer].”
The authors also note that “[r]egarding biomarker testing to determine the potential to benefit from specific therapies, the Panel limited recommendations to those assays that were evaluated by the FDA in the course of drug approval.”
They continue: “However, other assays may have comparable clinical utility for treatment selection, but a lack of comparative data limits the ability to recommend them.”
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