“Findings from the MONALEESA-3 trial dispelled the theory that a CDK4/6 inhibitor had to be reserved following recurrence on hormone therapy in postmenopausal patients with hormone receptor (HR)-positive, HER2-negative breast cancer, explained Dennis J. Slamon, MD, PhD.
“In the phase III trial, postmenopausal patients with HR-positive, HER2-negative advanced disease who received up to 1 prior line of therapy were randomized 2:1 to ribociclib (Kisqali) plus fulvestrant (Faslodex) or placebo.”
“The addition of the CDK4/6 inhibitor abemaciclib to fulvestrant significantly improved progression-free survival (PFS) and time to subsequent chemotherapy in pre- and perimenopausal women with hormone receptor–positive/HER2-negative advanced breast cancer, according to results from an analysis of the phase III MONARCH-2 trial (abstract 1002) presented at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting, held June 1–5 in Chicago.”
“The progression-free survival (PFS) benefit for ribociclib (Kisqali) in pre- or perimenopausal women with hormone receptor–positive, HER2-negative advanced or metastatic breast cancer was sustained across patient subgroups, according to findings from the phase III MONALEESA-7 trial presented at the 2018 Miami Breast Cancer Conference.
“MONALEESA-7 randomized patients to either the CDK4/6 inhibitor ribociclib in combination with tamoxifen or a nonsteroidal aromatase inhibitor (NSAI; letrozole or anastrozole) plus goserelin (n = 335), or to endocrine treatment plus goserelin (n = 337). Across the overall study population, the median PFS was 23.8 months for the ribociclib arm compared with 13.0 months for the control arm (HR, 0.553; 95% CI, 0.441-0.694; P <.0001).”
“According to findings published in Nature Communications, a blood test detecting early changes in circulating tumor DNA (ctDNA) may provide earlier indication of whether patients with hormone receptor–positive, HER2-negative breast cancer are responding to the CDK4/6 inhibitor palbociclib (Ibrance).
“The test could detect a response within 2 to 3 seeks, said investigators with The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust. Women currently wait 2 to 3 months to find out if palbociclib treatment is working for them.”
“Novartis’ CDK4/6 inhibitor Kisqali has picked up Breakthrough status in the US as an initial endocrine-based treatment in certain patients with breast cancer.
“The US Food and Drug Administration has awarded the designation for of pre- or perimenopausal women with hormone-receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) advanced or metastatic breast cancer in combination with tamoxifen or an aromatase inhibitor.”
“The combination of abemaciclib (Verzenio) and pembrolizumab (Keytruda) showed preliminary signs of activity without additive toxicity for patients with pretreated HR-positive, HER2-negative metastatic breast cancer, according to early results from a pilot trial presented in a poster at the 2017 San Antonio Breast Cancer Symposium (SABCS).
“At a 16-week analysis, the objective response rate (ORR) with the combination was 14.3%, which was less than the response rate seen with single-agent abemaciclib in the MONARCH-1 trial (19.7%). However, the trial investigators noted that the median time to response for abemaciclib has historically been 3.7 months, suggesting the efficacy is likely to improve with longer follow-up. At 16 weeks, the ORR in the MONARCH-1 trial was 6.8%.”
“At this year’s San Antonio Breast Cancer Symposium, several reports on new treatments for advanced breast cancer caught my attention. In an impressive analysis presented by Dr. Debu Tripathy, ribociclib (Kisqali, Novartis) extended progression-free survival (PFS) and improved the quality of life in young women with metastatic hormone receptor (HR) positive, HER2 negative tumors.
“Ribociclib meets ‘a clear and unmet need for premenopausal patients with HR positive, HER2 negative advanced breast cancer,’ Tripathy said at the press meeting in San Antonio. Novartis sponsored the MONALEESA-7 trial in which 672 eligible women with metastatic disease were randomized to receive hormone-blocking agents with either ribociclib or a placebo. The study registered women between age 25 and 58; the median age was around 44 years; the groups were divided evenly. The international study includes metastatic breast cancer patients in North and South America, Europe, Asia and Australia.”
“AstraZeneca’s Faslodex has been cleared on both sides of the Atlantic for use in combination with a CDK4/6 inhibitor.
“In the EU, the drug’s use has been approved for use alongside the CDK4/6 inhibitor palbociclib to treat a certain form of breast cancer, in the US it can be prescribed in combination with the CDK4/6 inhibitor abemaciclib.
“Both the European Commission and US Food and Drug Administration have approved the combination for the treatment of hormone receptor-positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) locally advanced or metastatic breast cancer in women who have received prior endocrine therapy.”
“Abemaciclib penetrated brain metastases and had antitumor activity in patients with hormone receptor (HR)-positive, HER2-negative metastatic breast cancer, preliminary evidence suggests.
“Results were presented in a poster at the 2017 ASCO Annual Meeting for 23 patients from a stage 1 efficacy analysis from a phase II study.
” ‘What we found were 2 patients who experienced partial responses within the CNS, suggesting there is activity of the agent in the brain and in patients who have HR-positive disease,’ explained lead author Sara M. Tolaney, MD, MPH.”