By: Jeff Minerd
New ASCO recommendations highlight genomic profiling and novel agents
ASCO has published two sets of updated guidelines for patients with human epidermal growth factor receptor 2 (HER2) negative breast cancer, both in the Journal of Clinical Oncology.
One of the updates (Burstein et al.) covers endocrine treatment and targeted therapy for patients with hormone receptor (HR) positive cancer. The other update (Moy et al.) covers chemotherapy and targeted therapy for patients with HR-negative disease or those who have already been treated with endocrine therapy.
n the following interview, Erica Mayer, MD, chair-elect of ASCO’s Cancer Communications Committee, summarizes some of the important changes and key themes of the new recommendations. Mayer is a medical oncologist and clinical investigator at Dana-Farber Cancer Institute in Boston.
The update by Burstein et al. endorses genomic profiling by tumor tissue or circulating tumor DNA for all patients. What is the intent of this recommendation?
Mayer: We have had the technology to obtain tumor genomic profiling for years, but until recently in breast cancer this information was primarily of scientific interest, but is not clinically actionable. As described by Burstein et al. and supported by the SOLAR-1 study, the approval of alpelisib [Piqray] for patients with metastatic ER+/HER2- PIK3CA-mutated cancers supports the need to obtain genomic profiling for all patients with ER+/HER2- advanced disease and identify best candidates for alpelisib. It is hoped that with further scientific progress, additional actionable genomic mutations will be identified as well.
That update also supports the use of endocrine therapy in combination with targeted therapies, including CDK4/6 inhibitors and alpelisib. How has this approach impacted the treatment of HER2-negative breast cancer?
Mayer: Historically, patients with ER+/HER2- breast cancer received endocrine therapies as sequential monotherapy. However, there are now substantial clinical trial data showing improved survival outcomes by partnering endocrine agents with a targeted agent, including CDK4/6 inhibitors in the first-line or pre-treated setting, and the PI3 kinase inhibitor alpelisib in pre-treated ER+/HER2- PIK3CA mutated breast cancer.
Overall, patients with metastatic ER+/HER2- breast cancer are living longer than ever before due to the benefits gained from adding in the targeted agents, and the new ASCO guidelines fully support this approach.
The update by Moy et al. includes several newer agents that have become available. Can you tell us about some of these and their indications?
Mayer: Management of triple-negative breast cancer — TNBC, cancer that is negative for ER/PR and HER2 receptors — has primarily involved use of chemotherapy. However, as described by Moy et al., there are now newer agents that are improving outcomes for patients with this subset of disease.
A subset of TNBC expresses the PD-L1 receptor, and as shown in the KEYNOTE-355 study, outcomes are improved when the PD-L1 inhibitor pembrolizumab is added to chemotherapy as part of first-line setting. In patients with metastatic TNBC and at least two prior lines of therapy for advanced disease, the antibody-drug conjugate sacituzumab govitecan significantly improves survival outcomes and is recommended.
Finally, in patients with germline BRCA1/2 mutations, a PARP inhibitor, such as olaparib or talazoparib, may be used in the first-line or pretreated metastatic HER2- breast cancer setting. Overall, the movement away from chemotherapy alone and towards treatment paradigms using targeted agents is welcome for this subset of disease.
Are there any general or overall themes in these updated guidelines?
Mayer: It has been incredibly heartening to see the advances from the cancer biology laboratory, including the ability to profile tumor mutations in real-time and understanding the mechanistic impact of genomic alterations, translate into clinically effective tools that provide benefit to patients living with advanced breast cancer.
The recent guidelines highlight the importance of learning as much as we can about each patient’s tumor, and then tailoring the treatment paradigm with inclusion of the appropriate agents. It is hoped that future drug approvals and guidelines will continue to reflect this successful translational science and ability to continue to personalize therapeutic strategies for each patient.
Read the study here.
Journal of Clinical Oncology
Source Reference: Burstein HJ, et al “Endocrine treatment and targeted therapy for hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer: ASCO guideline update” J Clin Oncol 2021; DOI: 10.1200/JCO.21.01392.
Journal of Clinical Oncology
Source Reference: Moy B, et al “Chemotherapy and targeted therapy for patients with human epidermal growth factor receptor 2–negative metastatic breast cancer that is either endocrine-pretreated or hormone receptor–negative: ASCO guideline update” J Clin Oncol 2021; DOI: 10.1200/JCO.21.01374.
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