Verzenio and Kisqali Deliver Positive Long-Term Results in Early Breast Cancer Trials

At the 2025 European Society for Medical Oncology (ESMO) Annual Meeting, Eli Lilly and Novartis each shared positive data from pivotal clinical trials evaluating their CDK4/6 inhibitors in early breast cancer.

Verzenio demonstrates overall survival benefit in monarchE trial

Lilly’s Verzenio (abemaciclib) alongside endocrine therapy (ET), being assessed in the Phase III monarchE trial (NCT03155997), reduced the risk of death by 15.8% compared to ET alone at two years. Additionally, treatment resulted in improvements across both invasive disease-free survival (IDFS) and distant relapse-free survival over seven years. The regimen was evaluated among participants with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-), node-positive, high-risk early breast cancer.¹

According to FirstWord Pharma, some doctors have had reservations around using Verzenio due to a lack of overall survival (OS) data. This latest readout showed a seven-year OS rate of 86.8% in the Verzenio treatment arm, versus 85% in the ET alone arm.²

In a press release, Stephen Johnston, MD, PhD, professor of breast cancer medicine and consultant medical oncologist at The Royal Marsden NHS Foundation Trust (London, UK) and lead investigator for monarchE, said: "For patients, survival is what matters most—and abemaciclib plus endocrine therapy represents the first contemporary medicine in over two decades to deliver a clear improvement in overall survival in the adjuvant setting. These results represent an important step forward in the treatment of high-risk HR+, HER2− early breast cancer."

monarchE trial design and analysis

Lilly’s monarchE trial is a global, randomized, open-label study that enrolled 5,637 adults across more than 600 sites in 38 countries.

• The trial included two cohorts: Cohort 1 (n=5,120) with ≥4 positive nodes or 1-3 nodes plus high-risk features (tumor ≥5 cm or Grade 3) and Cohort 2 (n=517) with 1-3 positive nodes and Ki-67 ≥20%.
• Participants were randomized 1:1 to receive Verzenio 150 mg twice daily plus adjuvant ET or ET alone for two years, with ET continued for at least five years if appropriate.
• The primary endpoint was IDFS, and OS was a key secondary endpoint.
• The OS analysis plan was later updated to extend follow-up and increase required events from 390 to 650 to ensure a more mature dataset.

Kisqali maintains durable benefit in NATALEE trial

Meanwhile, breaking data from Novartis’ Phase III NATALEE trial (NCT03701334) of Kisqali (ribociclib) revealed that treatment with Kisqali plus ET in patients with high-risk stage II and III HR+/HER2- early breast cancer resulted in a 28.4% reduction in risk of recurrence.³

Kisqali also saw long-term gains in this most recent analysis, demonstrating a five-year IDFS rate of 85% in the Kisqali plus ET arm, compared to 81.0% in the ET alone arm, representing a clinically meaningful improvement.

"For the thousands of people diagnosed with early breast cancer each year, the fear of recurrence, often as incurable advanced disease, weighs heavily on patients and their families," said Dr. John Crown, consultant medical oncologist at St. Vincent's University Hospital, Dublin, and NATALEE investigator, in a press release. "These five-year results show that the benefit of ribociclib persists well beyond the completion of treatment, offering these at-risk patients a greater chance of living breast cancer-free."

NATALEE trial design and outcomes

NATALEE is a global, randomized, open-label, trial conducted in collaboration with TRIO.

• The study enrolled 5,101 adults across 20 countries.
• ET in both arms consisted of a non-steroidal aromatase inhibitor (anastrozole or letrozole) with goserelin as indicated.
• The primary endpoint was IDFS, defined according to Standardized Definitions for Efficacy End Points (STEEP) criteria.
• The trial was designed to assess efficacy and safety in the broadest population of patients with HR+/HER2- early breast cancer.

References

1. Lilly's Verzenio® (abemaciclib) prolonged survival in HR+, HER2-, high-risk early breast cancer with two years of treatment. News release. Eli Lilly. October 17, 2025. Accessed October 20, 2025. https://investor.lilly.com/news-releases/news-release-details/lillys-verzenior-abemaciclib-prolonged-survival-hr-her2-high

2. Dennis, M. ESMO25: Battle lines drawn with updates for Lilly, Novartis CDK4/6 inhibitors. FirstWord Pharma. October 17, 2025. Accessed October 20, 2025. https://firstwordpharma.com/story/6323577

3. Novartis Kisqali® 5-year NATALEE data demonstrate 28% reduction in risk of recurrence in the broadest early breast cancer patient population. News release. Novartis. October 17, 2025. Accessed October 20, 2025. https://www.novartis.com/news/media-releases/novartis-kisqali-5-year-natalee-data-demonstrate-28-reduction-risk-recurrence-broadest-early-breast-cancer-patient-population