Dr McAndrew on a Subgroup Analysis of NATALEE in HR+/HER2– Early Breast Cancer

Nicholas P. McAndrew, MD, MSCE, hematologist-oncologist, assistant clinical professor, medicine, University of California, Los Angeles (UCLA), David Geffen School of Medicine, UCLA Medical Center, discusses a subgroup analysis of the phase 3 NATALEE trial (NCT03701334) and clinical outcomes in patients with hormone receptor–positive/HER2-negative early breast cancer by prior systemic treatment.

In the NATALEE trial, 5101 patients were randomly assigned 1:1 to receive an aromatase inhibitor (AI) alone or in combination with ribociclib (Kisqali) at 400 mg per day for 3 weeks on and 1 week off for 3 years. Men and premenopausal women also received goserelin. Patientswith stage IIA N0 disease required additional risk factors like grade 3 disease, high Ki-67 levels, or high genomic risk factors to be eligible for enrollment. Patients were grouped based on prior chemotherapy exposure and the duration of prior endocrine therapy.

Most patients enrolled in the NATALEE trial had received prior chemotherapy, as anticipated for this high-risk population, McAndrew begins. In total, 88.1% of patients had received prior chemotherapy, either in the neoadjuvant or adjuvant setting, with most receiving adjuvant therapy. The use of neoadjuvant chemotherapy is not typically standard in this population but can be administered under specific conditions, such as in patients with larger or more aggressive tumors, he expresses. Patients who received prior neoadjuvant chemotherapy represented the highest-risk group, yet they still benefited from the addition of ribociclib to an AI. Similarly, those who received prior adjuvant chemotherapy also experienced a benefit from ribociclib, McAndrew reports. The trial, however, was not designed to assess whether adding chemotherapy alone contributes to the benefit of ribociclib, though future analyses may explore this, he states.

Most patients (68.5%) had received prior systemic endocrine treatment. Importantly, those who had received endocrine therapy for at least 26 weeks (n = 711) did not have any differences in invasive disease-free survival compared with those who started therapy just months before enrollment, McAndrew expands. This finding provides reassurance to oncologists who prefer a gradual approach to initiating endocrine therapy, such as starting with tamoxifen followed by ovarian function suppression and an AI before introducing a CDK4/6 inhibitor in premenopausal patients, McAndrew emphasizes. This stepwise method, which is sometimes considered for patients who may struggle with symptoms when receiving endocrine therapy, does not negatively affect patient outcomes, according to McAndrew. The NATALEE analysis indicates that taking months to initiate endocrine therapy does not impedesurvival outcomes, he concludes