Press Release: Novartis Kisqali(R) NATALEE analysis reinforces consistent reduction in risk of recurrence across key subgroups of patients with early breast ...

-- Late-breaking NATALEE subgroup analysis to be presented at ESMO shows

invasive disease-free survival (iDFS) benefit remains consistent in all

subgroups, including in patients with stage II tumors, node-negative

disease and those who are 65 or older1

-- The data reinforce previously presented results which reported that

investigational use of Kisqali(R) (ribociclib) plus endocrine therapy

(ET) significantly lowered the risk of cancer recurrence across a broad

population of patients with stage II and III HR+/HER2- early breast

cancer (EBC), while also maintaining patients' quality of life in the

adjuvant setting1,2,3

-- The outcomes of patients treated with ET alone in this NATALEE analysis

confirm an unmet need across all study subgroups, including patients with

node-negative or stage II disease1

Basel, October 20, 2023 -- Novartis will present late-breaking results from a prespecified exploratory subgroup analysis of invasive disease-free survival (iDFS) from the pivotal Phase III NATALEE trial at the European Society for Medical Oncology (ESMO) Congress 2023. After 27.7 months of follow-up, the iDFS benefit with Kisqali(R) (ribociclib) plus endocrine therapy (ET) was consistent across key prespecified subgroups, compared to ET alone, in patients with stage II and III hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) early breast cancer (EBC) (see table below)(1). Results were also consistent with those in the overall trial population, reinforcing that the benefit was not driven by a specific patient subgroup(1) (,2).

iDFS results across key prespecified subgroups(1) :

Subgroup Treatment Arm, 3-year iDFS HR (95%

n rate, % CI)

-------------- --------------- ----------- ------------

AJCC Stage ribociclib + 94 0.76

II ET, 1011 91 (0.53-1.10)

ET alone, 1034

-------------- --------------- ----------- ------------

AJCC Stage ribociclib + 87 0.74

III ET, 1528 84 (0.59-0.93)

ET alone, 1512

-------------- --------------- ----------- ------------

N0 ribociclib + 94 0.63

ET, 285 89 (0.34-1.17)

ET alone, 328

-------------- --------------- ----------- ------------

N1-N3 ribociclib + 90 0.77

ET, 2261 87 (0.63-0.94)

ET alone, 2219

-------------- --------------- ----------- ------------

Premenopausal ribociclib + 91 0.72

women & men ET, 1126 89 (0.53-0.98)

ET alone, 1132

-------------- --------------- ----------- ------------

Postmenopausal ribociclib + 90 0.78

women ET, 1423 86 (0.61-1.00)

ET alone, 1420

-------------- --------------- ----------- ------------

<65 years ribociclib + 90 0.77

old ET, 2142 87 (0.62-0.94)

ET alone, 2186

-------------- --------------- ----------- ------------

>=65 years ribociclib + 90 0.72

old ET, 407 86 (0.46-1.14)

ET alone, 366

-------------- --------------- ----------- ------------

Ki-67 <=20% ribociclib + 92 0.80

ET, 1199 90 (0.59-1.08)

ET alone, 1236

-------------- --------------- ----------- ------------

Ki-67 >20% ribociclib + 89 0.75

ET, 920 84 (0.56-1.00)

ET alone, 938

-------------- --------------- ----------- ------------

"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 Aditya Bardia, M.D., Attending Physician, Medical Oncology, Mass General Cancer Center and Associate Professor, Medicine, Harvard Medical School and NATALEE trial investigator. "Given the outcomes of patients treated with endocrine therapy alone, this analysis outlines the potential benefit of adding ribociclib to endocrine therapy to reduce the risk of recurrence. 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."

"Despite endocrine therapy, cancer recurrence remains unpredictable, and too many patients diagnosed with stage II or III HR+/HER2- early breast cancer 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. "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."

Further analysis of the NATALEE trial is ongoing. Additional data, including the final efficacy analysis of the NATALEE trial, will be shared at upcoming medical meetings.

About NATALEE

NATALEE is a global Phase III multi-center, randomized, open-label trial to evaluate the efficacy and safety of ribociclib with ET as adjuvant treatment versus ET alone in patients with stage II and III HR+/HER2- EBC, being conducted in collaboration with TRIO(2). The adjuvant ET in both treatment arms was a non-steroidal aromatase inhibitor (NSAI; anastrozole or letrozole) and goserelin if applicable(2). The primary endpoint of NATALEE is iDFS as defined by the Standardized Definitions for Efficacy End Points (STEEP) criteria(2). A total of 5,101 adult patients with HR+/HER2- EBC across 20 countries were randomized in the trial(2).

Results previously announced at the American Society of Clinical Oncology (ASCO) Annual Meeting 2023 showed ribociclib plus ET, compared to ET alone, 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 benefit 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), post-menopausal women (HR=0.781; 95% CI: 0.613, 0.997)(2). Ribociclib data across all secondary efficacy endpoints was also consistent, including distant disease-free survival (DDFS) (26% risk reduction) and recurrence-free survival (RFS) (28% risk reduction), with a trend for improvement in overall survival (OS) (HR=0.759; 95% CI: 0.539, 1.068)(*) (2).

For these previously announced results, median study duration of follow-up was 34 months (range 21-48 months) with clinical benefits observed after approximately two years(2). NATALEE explored a lower starting dose (400 mg) of ribociclib than the dose approved for treatment in metastatic breast cancer (MBC) (600 mg) with the goal to minimize disruptions to patient quality of life without compromising efficacy. The safety profile of ribociclib at 400 mg was observed to have lower rates of symptomatic adverse events (AEs) and less need for dose modifications when administered up to three years(2). The most frequently reported AEs of special interest (grade 3 or higher) were neutropenia (43.8%) and liver-related AEs (e.g. elevated transaminases) (8.3%)(2).

*Results based on pre-specified interim analysis for OS at time of primary iDFS analysis; additional follow-up is planned to obtain more mature OS data(2).

About Early Breast Cancer

More than 90% of patients diagnosed with breast cancer have EBC(4). Despite adjuvant ET, approximately one-third of those diagnosed with stage II and more than half of those diagnosed with stage III HR+/HER2- EBC experience cancer recurrence(5) (,) (6). The risk of recurrence continues over decades with more than half of breast cancer recurrences occurring five or more years after diagnosis(5) (,) (7). For many of these patients, there are currently no targeted therapeutic options outside of the standard chemotherapy and ET(8).

About Kisqali(R) (ribociclib)

Kisqali has consistently demonstrated OS benefit while preserving or improving quality of life across three Phase III trials in MBC(9-20). Updates to the NCCN Guidelines(R) for breast cancer, released in January 2023, recommend ribociclib (Kisqali) as the only Category 1 preferred CDK4/6 inhibitor for first-line treatment of patients with HR+/HER2- MBC when combined with an aromatase inhibitor (AI)(2) (1). Additionally, Kisqali has the highest rating of any CDK4/6 inhibitor on the ESMO Magnitude of Clinical Benefit Scale, achieving a score of five out of five for first-line pre-menopausal patients with HR+/HER2- advanced breast cancer(2) (2). Further, Kisqali in combination with either letrozole or fulvestrant has uniquely, among other CDK4/6 inhibitors, received a score of four out of five for post-menopausal patients with HR+/HER2- advanced breast cancer treated in the first line(2) (3).

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