Ribociclib With Endocrine Therapy Improved Invasive Disease-Free Survival in Patients With Early Breast Cancer


Compared to endocrine therapy alone, the combination of ribociclib and endocrine therapy lowered the risk of cancer recurrence in patients with early breast cancer by 25.2%.

The phase 3 trial NATALEE results demonstrate an improvement in invasive disease-free survival (iDFS) after 27.7 months of follow-up in patients with stage II and III hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) early breast cancer (EBC) who received the CDK4/6 inhibitor ribociclib (Kisqali; Novartis) plus enocrine therapy (ET) as treatment. The results were presented at the 2023 European Society for Medical Oncology (ESMO) Congress.

Health care worker looking at a mammogram

Image credit: Valerii Apetroaiei | stock.adobe.com

Ribociclib has been approved by the FDA for the treatment of adult patients with HR+/HER2- advanced or metastatic breast cancer (MBC) in combination with an aromatase inhibitor (AI) as initial ET or fuvlestrant as initial ET or following disease progression on ET in post-menopausal women or men. Ribociclib is the only category 1 preferred CDK4/6 inhibitor for first-line treatment of patients with HR+/HER2- MBC when combined with an AI.

NATALEE is a global, multi-center, randomized, open-label phase 3 trial that compared the efficacy and safety of ribociclib with ET as adjuvant treatment with ET alone in patients with stage II and III HR+/HER2- EBC. The adjuvant ET in both treatment groups was a non-steroidal aromatase inhibitor (NSAI; anastrozole or letrozole) and goserelin. A total of 5101 adult patients across 20 countries were enrolled in the study and the primary endpoint was iDFS.

“Despite ET, cancer recurrence remains unpredictable, and too many patients diagnosed with stage II or III HR+/HER2- EBC experience their cancer coming back. This analysis further reinforces the potential of ribociclib to address the need for a new adjuvant option that reduces the ongoing risk of recurrence consistently across many types of at-risk patients,” said Jeff Legos, executive vice president, global head of oncology development at Novartis, in a press release.

The results showed that compared to ET alone, ribociclib plus ET lowered the risk of cancer recurrence by 25.2% (HR=0.748; 95% CI: 0.618, 0.906; p=0.0014) along with consistent clinically meaningful iDFS across key pre-specified subgroups: AJCC Tumor Stage II (HR=0.761; 95% CI: 0.525, 1.103), AJCC Tumor Stage III (HR=0.740; 95% CI: 0.592, 0.925), node-negative disease (HR=0.630; 95% CI: 0.341, 1.165), node-positive disease (HR=0.771; 95% CI: 0.630, 0.944), pre-menopausal women and men (HR=0.722; 95% CI: 0.530, 0.983), and post-menopausal women (HR=0.781; 95% CI: 0.613, 0.997).

“Subgroup analyses provide a more comprehensive picture of clinical benefit for patients and are critical to guiding treatment decisions, as they help indicate how different breast cancer subgroups might respond to treatment,” said NATALEE trial investigator Aditya Bardia, MD, Attending Physician, Medical Oncology, Mass General Cancer Center and Associate Professor, Medicine, Harvard Medical School, in the press release.

Ribociclib data across all secondary efficacy endpoints was also consistent, including overall survival (OS), distant disease-free survival (DDFS) and recurrence-free survival (RFS) with risk reductions of 26% and 28%, respectively. Further, the results were consistent with those in the overall trial population, indicating that the benefit was not driven by the specific patient subgroup alone.

“Given the outcomes of patients treated with ET alone, this analysis outlines the potential benefit of adding ribociclib to ET to reduce the risk of recurrence,” said Bardia in the press release. “These data provide important insight into how we think about residual risk in this population and make adjuvant treatment decisions for patients with localized breast cancer.”

The median follow-up duration was 24 months (range 21 to 48 months) with clinical benefits observed over the course of 2 years. NATALEE used a lower starting dose of 400 mg of ribociclib than the dose approved for MBC, which is 600 mg. The goal was to minimize disruptions to the patients’ quality of life without hindering efficacy. At 400 mg, the safety profile of ribociclib was shown to have lower rates of symptomatic adverse events (AEs) and less need for dose modifications when administered for up to 3 years. The most common grade 3 or higher AEs reported were neutropenia (43.8%) and liver-related complications (8.3%).

“These results from the NATALEE trial add to the wealth of efficacy, safety and quality of life data suggesting that ribociclib, if approved, could provide healthcare providers with a new option to help keep their patients living well and cancer-free,” Legos said in the press release.


Novartis. Novartis Kisqali® NATALEE analysis reinforces consistent reduction in risk of recurrence across key subgroups of patients with early breast cancer. News release. October 20, 2023. Accessed October 20, 2023. https://www.novartis.com/news/media-releases/novartis-kisqali-natalee-analysis-reinforces-consistent-reduction-risk-recurrence-across-key-subgroups-patients-early-breast-cancer

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