Ribociclib Demonstrates Promising OS Benefit in HR+/HER2- Advanced Breast Cancer

Combination of ribociclib plus fulvestrant achieved a median overall survival of 67.6 months in the first-line setting for patients with postmenopausal, hormone receptor-positive, human epidermal growth factor receptor-2 negative advanced or metastatic breast cancer.

Ribociclib (Kisqali) plus fulvestrant (Faslodex) achieved a median overall survival (OS) of 67.6 months in the first-line setting for postmenopausal patients with hormone receptor-positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) advanced or metastatic breast cancer, according to a press release issued by Novartis.1

Data comes from the updated exploratory OS analysis of the phase 3 MONALEESA-3 study (NCT02422615), which is set to be presented at the 2022 European Society of Medical Oncology Breast Cancer Congress.

“MONALEESA-3 results continue to demonstrate the survival benefit of treatment with ribociclib for postmenopausal women with advanced breast cancer,” stated Dennis J. Slamon, MD, director of clinical/translational research, University of California, Los Angeles Jonsson Comprehensive Cancer Center, in the press release. “Whether partnered with fulvestrant or an aromatase inhibitor in the first-line setting, ribociclib offers oncologists a CDK4/6 inhibitor with consistent benefit in providing women with HR+/HER2- advanced breast cancer more quality time, regardless of their disease characteristics.”

Currently, ribociclib is the only CDK4/6 inhibitor-fulvestrant combination to show benefit in OS benefit in the first-line setting. Ribociclib is also the CDK4/6 inhibitor with the longest median OS reported and that has consistent OS benefit across 3 phase 3 trials, despite combination partner, line of therapy, menopausal status, or site and number of metastases.

The multicenter, randomized, double-blind, placebo controlled MONALEESA-3 study evaluated a total of 726 postmenopausal men and women with HR-positive, HER2-negative advanced breast cancer.2

Patients were randomized 2:1 to receive either ribociclib at 600 mg daily in a 3-weeks-on/1-week-off schedule plus fulvestrant at 500 mg daily or a matching dose of placebo. Patients were stratified by the presence or absence of liver or lung metastases and prior endocrine therapy.

Enrollment was open to patients aged 18 years and older with a histologically and/or cytologically confirmed diagnosis of estrogen-receptor positive and/or progesterone receptor positive breast cancer by local laboratory and HER2-negative breast cancer. Female patients required to be postmenopausal and other requirements included the patient having measurable disease by RECIST 1.1 or at least 1 predominantly lytic bone lesion, advanced breast cancer, an ECOG performance status of 0 or 1, and adequate bone marrow and organ function.

The primary end point was locally assessed PFS per RECIST v1.1 criteria with secondary end points including OS, overall response rate, clinical benefit rate, time to response, duration of response, time to definitive deterioration of ECOG performance status, patient-reported outcomes, safety, and pharmacokinetics.

The exploratory analysis of MONALEESA-3 evaluated patients for a median of 71 months, which was over 2 years of follow-up from the final key secondary end point OS analysis. The final OS analysis showed ribociclib plus fulvestrant to demonstrate a statistically significant OS benefit as well as a relative reduction in the risk of death by 28% compared to fulvestrant alone in the full population (HR, 0.72; 95% CI, 0.568-0.924; P =0.00455).

With a median follow up of 5 years, the updated analysis found that in the first-line, ribociclib plus fulvestrant (n = 237) achieved 67.6 months median OS vs 51.8 months for those treated with fulvestrant alone (n = 128) (HR, 0.673; 95% CI, 0.504-0.899). Additionally, the combination of ribociclib plus fulvestrant vs patients on fulvestrant alone experienced over 1-and-a-half years of additional delay to subsequent use of chemotherapy (49.2 months vs 29.0 months, HR, 0.624; 95% CI, 0.481-0.810).

For women who received the combination of ribociclib and fulvestrant, the estimated survival rate at 5 years was 56.5% (95% CI, 49.5-62.9) vs 42.1% (95% CI, 33.2-50.7) for those who received fulvestrant alone. A total of 16.5% of patients in the combination arm (n = 39) compared to 8.6% of those in the fulvestrant only arm (n = 11) continued therapy at this longer follow-up. Additionally, no new adverse events were observed.

“It is a tremendous achievement to see such remarkable, consistent overall survival results from the MONALEESA clinical trial program, demonstrating how Novartis is transforming care for people with breast cancer as we continue to work toward cures,” added Jeff Legos, executive vice president, global head of oncology & hematology development, in the press release. “The unique profile of Kisqali continues to be reinforced, with results from MONALEESA-3 pushing the boundaries of how using a Kisqali-combination treatment regimen can extend lives of postmenopausal women living with HR+/HER2- advanced breast cancer without compromising quality of life.”

  1. New Novartis data demonstrate only Kisqali® offers more life in the first-line setting for postmenopausal HR+/HER2- advanced breast cancer patients. Novartis. News Release. May 4, 2022. Accessed May 4, 2022. https://bit.ly/3w5FVgU
  2. Study of efficacy and safety of LEE011 in men and postmenopausal women with advanced breast cancer. (MONALEESA-3). Clinicaltrials.gov. Accessed May 4, 2022. https://clinicaltrials.gov/ct2/show/NCT02422615
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