Selection of Optimal Adjuvant Chemotherapy and Targeted Therapy for Early Breast Cancer

Rapid Recommendation Update

Published Online April 24, 2024

Recommendation 1 

Abemaciclib for 2 years plus ET for ≥ 5 years may be offered to patients meeting the criteria of the ITT monarchE population with resected, hormone receptor-positive, HER2-negative, node-positive, early breast cancer at high risk of recurrence, defined as having ≥ 4 positive axillary lymph nodes (ALNs) or as having 1-3 positive ALNs plus at least one of the following features: grade 3 disease, tumor size ≥ 5 cm, or Ki-67 index ≥ 20%. Although the FDA’s language is broad, the Panel promotes the use of abemaciclib primarily in those who would have been eligible for monarchE based on that trial’s eligibility criteria.

Recommendation 2

The Panel recommends, based on the phase III NATALEE trial, that adjuvant ribociclib (400 mg once daily, 3 weeks on followed by 1 week off) for 3 years plus ET may be offered to patients with anatomic stage II or III breast cancer who would have met criteria for study entry and have a high risk of recurrence.

Qualifying statements for Recommendations 1 and 2 on the use of adjuvant abemaciclib and ribociclib: The Panel believes that adjuvant CDK4/6 inhibitor therapy may not provide meaningful clinical benefit to all patients who would have been eligible for the available trials, especially the lower-risk patients who were included in the NATALEE trial. For example, for most patients with node-negative disease, the risks of ribociclib may outweigh the benefits, with the exception of some patients with the highest risk, node-negative disease.  However, the Panel acknowledges that there are insufficient data to specify which subgroups of patients do or do not warrant therapy. The Panel thus recommends considering the benefits, risks, costs, and preferences for each individual patient when deciding whether to recommend therapy.  Among patients meeting criteria for both monarchE and NATALEE, the Panel also notes that, of the two CDK4/6 inhibitors, abemaciclib has longer follow-up, a deepening benefit over time, a shorter duration of therapy, and FDA approval in the adjuvant setting. In this case, the Panel favors using abemaciclib, reserving use of ribociclib in patients who have a contraindication to (e.g., pre-existing high-grade diarrhea) or intolerance of abemaciclib. The Panel characterized the strength of the ribociclib recommendation as conditional, pending future efficacy data and regulatory updates. Although a formal cost-effectiveness analysis was out of scope for this update, it could be informative for some decision-makers considering the costs of both medications. Results from longer-term follow-up will further inform adjuvant therapy decision-making.  

Rapid Recommendation Update

Published Online November 15, 2021

Updated Recommendation: Based on a secondary pre-defined analysis conducted by the FDA , two years of abemaciclib (150 mg twice daily) plus ET may be offered to patients with HR-positive, HER2-negative, node-positive early breast cancer with a high risk of recurrence and a Ki-67 score of  ≥20% as determined by an FDA-approved test. (Type: evidence-based, benefits outweigh harms; Evidence quality: moderate; Strength of recommendation: strong). 

Published online before print October 20, 2020, DOI: 10.1200/JCO.20.02510

Neelima Denduluri, MD; Mark R. Somerfield, PhD; Mariana Chavez-MacGregor, MD, MSc; Amy H. Comander, MD; Zoneddy Dayao, MD; Andrea Eisen, MD; Rachel A. Freedman, MD, MPH; Ragisha Gopalakrishnan, MD; Stephanie L. Graff, MD; Michael J. Hassett, MD, MPH; Tari A. King, MD; Gary H. Lyman, MD, MPH; Gillian Rice Maupin, JD; Raquel Nunes, MD; Cheryl L. Perkins, MD, RPh; Melinda L. Telli, MD; Maureen E. Trudeau, MD; Antonio C. Wolff, MD; and Sharon H. Giordano, MD, MPH

Purpose

The aim of this work is to update key recommendations of the ASCO guideline adaptation of the Cancer Care Ontario guideline on the selection of optimal adjuvant chemotherapy regimens for early breast cancer and adjuvant targeted therapy for breast cancer.

Methods

An Expert Panel conducted a targeted systematic literature review guided by a signals approach to identify new, potentially practice-changing data that might translate into revised guideline recommendations.

Results

The Expert Panel reviewed abstracts from the literature review and identified one article for inclusion that reported results of the phase III, open-label KATHERINE trial. In the KATHERINE trial, patients with stage I to III human epidermal growth factor receptor 2 (HER2)–positive breast cancer with residual invasive disease in the breast or axilla after completing neoadjuvant chemotherapy and HER2-targeted therapy were allocated to adjuvant trastuzumab emtansine (T-DM1; n = 743) or to trastuzumab (n = 743). Invasive disease–free survival was significantly higher in the T-DM1 group than in the trastuzumab arm (hazard ratio, 0.50; 95% CI, 0.39 to 0.64; P < .001), and risk of distant recurrence was lower in patients who received T-DM1 than in patients who received trastuzumab (hazard ratio, 0.60; 95% CI, 0.45 to 0.79). Grade 3 or higher adverse events occurred in 190 patients (25.7%) who received T-DM1 and in 111 patients (15.4%) who received trastuzumab.

Recommendations

Patients with HER2-positive breast cancer with pathologic invasive residual disease at surgery after standard preoperative chemotherapy and HER2-targeted therapy should be offered 14 cycles of adjuvant T-DM1, unless there is disease recurrence or unmanageable toxicity. Clinicians may offer any of the available and approved formulations of trastuzumab, including trastuzumab, trastuzumab and hyaluronidase-oysk, and available biosimilars.

© 2020 American Society of Clinical Oncology, all rights reserved. For licensing opportunities, contact licensing@asco.org. 

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