Ribociclib ups PFS in Asian women with advanced breast cancer
Adding ribociclib to aromatase inhibitor letrozole significantly improves progression-free survival (PFS) in postmenopausal Asian women with advanced breast cancer, according to a sub-analysis of the MONALEESA-2 study presented at the ESMO Asia 2016 Congress in Singapore.
Asian patients (n=68) treated with ribociclib and letrozole achieved clinically meaningful PFS benefit whether categorized by geographic region or race (PFS improvement 70 and 61 percent, respectively). [ESMO Asia 2016 Congress, abstract LBA1]
“Ribociclib combined with letrozole was well tolerated in Asian patients, with similar safety profile observed for the full cohort,” said study author Dr
Yoon-Sim Yap, senior consultant in the Department of Medical Oncology at National Cancer Centre Singapore.
Discussing the potential implications of the findings on clinical practice, Associate Professor Rebecca Dent, senior consultant Medical Oncology at National Cancer Centre Singapore, said: “CDK4/6 inhibitors are certainly changing the landscape in HR-positive breast cancer. They have broad-spectrum activity independent of the disease-free interval, the site, the volume, the ethnicity.”
There is minimal and manageable toxicity, avoidance of intravenous therapy and maintenance of quality of life, she added. “And this is in young women with advanced disease and large pleural effusions where we can get away with life-disrupting chemotherapy and offer oral therapy, allowing them to attend to their children and spend less time in the chemotherapy suite.”
Combination therapy with a CDK4/6 inhibitor
Endocrine therapy is the preferred option for first-line treatment of HR-positive, HER2-negative advanced breast cancer. However, endocrine resistance is common and disease progression eventually occurs, Yap said. Single-agent endocrine therapy may not be enough to delay advanced metastatic disease.
“We need novel therapies to improve treatment outcomes for patients considering that
24 percent of breast cancer worldwide are diagnosed in Asia, Yap said. “We really have to address endocrine resistance,” Dent added.
The phase III MONALEESA-2 study compared the CDK4/6 inhibitor ribociclib plus letrozole vs letrozole plus placebo in 668 women with HR-positive, HER2-negative recurrent or metastatic breast cancer who had not received previous systemic therapy for advanced disease. All women received ribociclib 600 mg daily (on a 3-weeks-on, 1-week-off schedule) and letrozole 2.5 mg daily or placebo plus letrozole. PFS was the primary endpoint of the study, overall survival, overall response rate and safety, the secondary endpoints. Investigators presented the study’s interim results at ESMO 2016 Congress in Copenhagen, Denmark in October 2016.
Supportive PFS analyses were conducted in prespecified patient subsets, including in Asian patients (n=68) treated in Taiwan, Singapore, Thailand, and South Korea. Two-thirds of the patients (n=51) were Asians by race.
Similar with results from the Asian subgroups, the combination of ribociclib and letrozole prolonged PFS (hazard ratio [HR], 0.56 (p= 3.29 x 10-6 for superiority) in the full population of patients with HR-positive, HER2-negative disease in the MONALEESA-2 study. This translates to a 44 percent reduction in the risk of disease progression or death during a median follow-up of 15.3 months. After 18 months, PFS rate was 63 percent with ribociclib vs 42.2 percent with placebo. The overall response rate was 52.7 and 37.1 percent, respectively (p<0.001) in patients with measurable disease at baseline. [N Engl J Med 2016;375:1738-1748]
New option for HR-positive, HER2-negative disease
Speaking at the ESMO 2016 Congress in Denmark, discussant Professor Stephen Johnston of the Royal Marsden Hospital NHS Foundation Trust in London, UK then noted the “impressive separation of curves early in the treatment,” leading to significant improvement in benefit and efficacy.
The most common grade 3/4 adverse events reported in over 10 percent of ribociclib and placebo patients were neutropenia (59.3 vs 0.9 percent) and leukopenia (21 vs 0.6 percent. Discontinuation rates because of adverse events were 7.5 and 2.1 percent, respectively. [N Engl J Med 2016;375:1738-1748]
Dr Sing-Huang Tan, senior consultant, Department of Haematology-Oncology, National University Cancer Institute, Singapore (NCIS), who is not affiliated with the study, said the subgroup analysis provides further evidence that ribociclib in combination with letrozole demonstrates similar efficacy in Asians. “It highlights another alternative to the various therapies already available, and may serve as an additional combination therapeutic option for patients with a higher burden of disease for which endocrine therapy is still deemed appropriate.”
The use of this combination treatment could be practice changing, she said, but cautioned that cost and drug availability may hinder its use in certain parts of Asia when ribociclib is approved.
“The data at hand are promising, but we have to wait for the overall survival results specifically in the Asian subset of patients in MONALEESA-2,” Dent concluded.
In the meantime, more research and excellent clinical judgment are warranted to determine which patients with advanced breast cancer should be targeted for combination therapy or primary endocrine therapy alone.