Endocrine Treatment and Targeted Therapy for Hormone Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Metastatic Breast Cancer: ASCO Guideline Update

Abstract

PURPOSE To update recommendations of the ASCO systemic therapy for hormone receptor (HR)-positive metastatic breast cancer (MBC) guideline. METHODS An Expert Panel conducted a systematic review to identify new, potentially practice-changing data. RESULTS Fifty-one articles met eligibility criteria and form the evidentiary basis for the recommendations. RECOMMENDATIONS Alpelisib in combination with endocrine therapy (ET) should be offered to postmenopausal patients, and to male patients, with HR-positive, human epidermal growth factor receptor 2 (HER2)-negative, PIK3CA-mutated, ABC, or MBC following prior endocrine therapy with or without a cyclin-dependent kinase (CDK) 4/6 inhibitor. Clinicians should use next-generation sequencing in tumor tissue or cell-free DNA in plasma to detect PIK3CA mutations. If no mutation is found in cell-free DNA, testing in tumor tissue, if available, should be used as this will detect a small number of additional patients with PIK3CA mutations. There are insufficient data at present to recommend routine testing for ESR1 mutations to guide therapy for HR-positive, HER2-negative MBC. For BRCA1 or BRCA2 mutation carriers with metastatic HER2-negative breast cancer, olaparib or talazoparib should be offered in the 1st-line through 3rd-line setting. A nonsteroidal aromatase inhibitor (AI) and a CDK4/6 inhibitor should be offered to postmenopausal women with treatment-naïve HR-positive MBC. Fulvestrant and a CDK4/6 inhibitor should be offered to patients with progressive disease during treatment with AIs (or who develop a recurrence within 1 year of adjuvant AI therapy) with or without one line of prior chemotherapy for metastatic disease, or as first-line therapy. Treatment should be limited to those without prior exposure to CDK4/6 inhibitors in the metastatic setting. Additional information can be found at www.asco.org/breast-cancer-guidelines .

Major advancements in metastatic breast cancer treatment: when expanding options means prolonging survival

“…Furthermore, the establishment of a state of endocrine resistance and the exhaustion of endocrine-based strategies represent clinical scenarios where chemotherapy is still commonly used. 39 , 40 , 41 …”

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

“…• Endocrine Therapy and Targeted Therapy for Hormone Receptor-Positive, HER2-negative Metastatic Breast Cancer 13 The following represents disclosure information provided by the authors of this manuscript. All relationships are considered compensated unless otherwise noted.…”

Endocrine Treatment for Breast Cancer Patients Revisited—History, Standard of Care, and Possibilities of Improvement

“…However, in contrast to the above-mentioned substances, with alpelisib a PI3K inhibitor is available for the PIK3CA-mutated, postmenopausal aBC patient, since it shows a statistically significant benefit regarding PFS as well as a meaningful clinical benefit in OS, with an acceptable safety profile at the same time [ 49 , 50 , 51 , 52 ]. Its approval is the result of the SOLAR-1 trial, based on which, in current treatment guidelines, the substance is recommended for the therapy of women as well as men with this specific tumor type [ 53 ]. Further trials with different treatment combination strategies including CDK4/6 inhibitors, fulvestrant, and alpelisib or novel PI3K inhibitors, such as inavolisib and copanlisib, or even combined PI3K/mTOR inhibitors, such as gedatolisib for instance, will deliver more information about the efficacy and safety of this drug family [ 54 , 55 , 56 ].…”

“…On the basis of this effect, the further development of CDK4/6 inhibition started [ 63 , 64 ]. In the past few years, the CDK4/6 inhibitors palbociclib, ribociclib, and abemaciclib have been approved and recommended [ 53 ] for the treatment of hormone-receptor-positive, HER2-negative aBC on the basis of three large phase III trial programs, PALOMA, MONALEESA, and MONARCH, since all trials show a significant improvement in PFS when combined with an AI or fulvestrant [ 65 , 66 , 67 , 68 , 69 , 70 , 71 ] ( Table 1 ). Regarding PFS, CDK4/6 inhibitors in the first and second treatment lines are also superior compared to chemotherapy [ 72 ], hence their use increased substantially in the first years after becoming available, while fewer patients started receiving chemotherapy [ 73 , 74 ].…”