NATALEE (TRIO033) Phase III trial demonstrates ribociclib significantly reduces the risk of recurrence for patients with early breast cancer, at interim analysis

March 31, 2023

Translational Research In Oncology (TRIO) today announced positive topline results from NATALEE (TRIO033), a Novartis sponsored Phase III trial of ribociclib plus endocrine therapy (ET) as adjuvant treatment for patients with stages II and III early breast cancer (EBC) at risk of disease recurrence. NATALEE (TRIO033) met its primary endpoint at a pre-planned interim analysis, achieving a statistically significant improvement in invasive disease-free survival (iDFS) in women and men with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) EBC, when compared to ET alone.

“At TRIO, we always strive to improve the lives of cancer patients by conducting clinical trials that might make a fundamental difference in outcomes. We are very proud of our collaboration with Novartis in the conduct of the NATALEE (TRIO033) trial. The results announced today are a significant step forward towards reducing the risk of cancer recurrence in HR+/HER2- early breast cancer” said Catherine Marle, TRIO Chief Executive Officer.

“The NATALEE trial was designed to evaluate a broad spectrum of early breast cancer patients, including those with stages II and III for whom there are few therapies to reduce the risk of recurrence,” said Dennis J. Slamon, MD, Director of Clinical/Translational Research, University of California, Los Angeles Jonsson Comprehensive Cancer Center, Chairman and Executive Director of TRIO, and NATALEE (TRIO033) trial lead investigator. “While the risk of relapse in these patients is highest within 2-3 years after diagnosis, many early breast cancer patients face the risk of disease recurrence throughout several years. Given the limited advancements in reducing the risk of breast cancer recurrences while maintaining quality of life for patients diagnosed with early breast cancer, it’s extremely encouraging to see that this study has met its primary endpoint and achieved these goals.”

NATALEE is a Novartis sponsored, global Phase III multi-center, randomized, open-label trial to evaluate the efficacy and safety of ribociclib with endocrine therapy as adjuvant treatment versus endocrine therapy alone in patients with HR+/HER2- EBC. The primary endpoint of NATALEE is invasive disease-free survival (iDFS) and secondary endpoints include safety, quality of life, and overall survival, among others. More than 5,100 adult patients with HR+/HER2- were randomized in the trial, including patients with tumor Stages IIA, IIB or III EBC, irrespective of nodal status. Node negative patients with Stage IIA needed to have tumors that were Grade 2-3 or with Ki67 above 20% or high-risk gene expression. NATALEE explored a lower starting dose (400mg) of ribociclib than the dose evaluated and approved for treatment in the metastatic setting (600mg). Treatment with ribociclib lasted 36 months whereas treatment with ET (in both arms) lasted 60 months while on study.

About TRIO
TRIO is a full-service oncology CRO that brings a unique blend of academic leaders, a global network of investigators and patient advocates, along with an experienced and passionate clinical development team. Our mission is to change the lives of cancer patients by conducting clinical trials that make a difference. We are an engaged partner for industry, academia and patients and are aimed at accelerating effective drug development. Additional information on TRIO can be found by visiting

Catherine Marle
Chief Executive Officer
Translational Research in Oncology