Ribociclib Plus Endocrine Therapy Meets iDFS End Point in HR+ Early Breast Cancer

The combination of ribociclib (Kisqali) and endocrine therapy (ET)significantly reduced the risk of disease recurrence vs standard adjuvant ET in patients with hormone receptor–positive/HER2-negative early breast cancer at risk of recurrence, meeting the primary end point of the phase 3 NATALEE trial (NCT03701334).¹

Notably, consistent benefit was observed in those with stage II and III disease, irrespective of nodal involvement. Because the primary end point of invasive disease-free survival (iDFS) was met, the Independent Data Monitoring Committee has recommended to stop the trial early.

In accordance with the trial protocol, follow-up will continue to assess long-term outcomes.

“There is a critical need for new, well-tolerated options that keep patients cancer free without disrupting quality of life,” Dennis J. Slamon, MD, lead trial investigator and director of Clinical/Translational Research at the University of California, Los Angeles Jonsson Comprehensive Cancer Center and chairman and executive director of Translational Research in Oncology, stated in a press release. “The NATALEE trial, where ribociclib was given for 3 years plus ET, was designed with these unmet needs in mind, and it is extremely encouraging that this study met its primary end point.”

The open-label, multicenter, randomized phase 3 trial enrolled patients with histologically confirmed unilateral primary invasive adenocarcinoma of the breast, estrogen or progesterone receptor positivity and HER2 negativity.² Patients were required to be at least 18 years of age, have available archival tumor tissue from the surgical specimen, and an ECOG performance status of 0 or 1.

Patients could not have previously received a CDK4/6 inhibitor; tamoxifen, raloxifene, or aromatase inhibitors for breast cancer risk reduction and/or treatment for osteoporosis within the past 2 years before randomization; or anthracyclines at cumulative doses of 450 mg/m2 or more for doxorubicin or 900 mg/m2 or more for epirubicin. Other exclusion criteria include having distant metastases beyond the regional lymph nodes, concurrent use of other antineoplastic therapy except for adjuvant ET and having undergone major surgery, chemotherapy, or radiotherapy within 2 weeks of randomization, among others.

Study participants were randomly assigned to receive ribociclib at a daily dose of 400 mg on days 1 to 21 of a 28-day cycle followed by 7 days off, and ET given once daily and continuously or ET given once daily continuously. Notably, ribociclib was evaluated at a lower starting dose than the 600-mg dose approved for metastatic breast cancer treatment to reduce disruptions to quality of life (QOL) without compromising efficacy.

In addition to the primary end point of iDFS by Standardized Definitions for Efficacy End Points criteria, key secondary end points included recurrence-free survival, distant disease-free survival, overall survival, QOL, and pharmacokinetics.

“The positive topline results from NATALEE represent a major milestone in our ambition to expand the benefits of [ribociclib] to patients with earlier stages of breast cancer, building on the heritage of this effective treatment in hormone receptor–positive/HER2-negative metastatic breast cancer,” Shreeram Aradhye, MD, president of Global Drug Development and chief medical officer at Novartis, added in the press release. “These data have the potential to be paradigm-shifting for patients at risk of recurrence, including those with no nodal involvement, who have limited well-tolerated options to prevent recurrence. Our teams are working on submissions to health authorities around the world with the hope to bring [ribociclib to many more patients diagnosed with breast cancer.”

References

1. Novartis Kisqali phase III NATALEE trial meets primary endpoint at interim analysis demonstrating clinically meaningful benefit in broad population of patients with early breast cancer. News release. Novartis. March 27, 2023. Accessed March 27, 2023. https://www.novartis.com/news/media-releases/
2. A trial to evaluate efficacy and safety of ribociclib with endocrine therapy as adjuvant treatment in patients with HR+/HER2- early breast cancer (NATALEE). ClinicalTrials.gov. Updated December 30, 2022. Accessed March 27, 2023. https://clinicaltrials.gov/ct2/show/NCT03701334