Ribociclib-fulvestrant combo improves PFS in HR+/HER2- advanced breast cancer
The combination of ribociclib, a CDK*4/6 inhibitor, and fulvestrant significantly improves progression-free survival (PFS) in post-menopausal women with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer, according to the MONALEESA-3** study presented at ASCO 2018.
“Ribociclib and fulvestrant may represent a new therapeutic option in this subtype of advanced breast cancer, both for patients receiving treatment in the first-line … [and] second-line setting[s],” said lead author Dr Dennis J. Slamon from the University of California, Los Angeles (UCLA) Medical Center in Santa Monica, California, US.
This phase III, double-blind trial involved 726 post-menopausal women (median age 63 years) with HR+/HER2- advanced breast cancer who were randomized in a 2:1 ratio to receive oral ribociclib (600 mg/day on a 3-week-on, 1-week-off schedule) plus intramuscular fulvestrant (500 mg on day 1 of each 28-day cycle) or placebo plus fulvestrant (fulvestrant only group). Tumour response assessments were performed every 8 weeks for 18 months and subsequently every 12 weeks. [ASCO 2018, abstract 1000]
Compared with women who received fulvestrant only, women treated with ribociclib + fulvestrant had significantly improved PFS (210 vs 151 events; median, 20.5 vs 12.8 months, hazard ratio [HR], 0.593, 95 percent confidence interval [CI], 0.480– 0.732; p<0.001).
When 40 percent of the patients were randomly assessed by the BIRC***, results also showed improved PFS among women in the ribociclib + fulvestrant group over the fulvestrant only group (median, not reached vs 10.9 months, HR, 0.492, 95 percent CI, 0.345–0.703).
In a subgroup analysis of PFS by prior endocrine therapy status, a significantly better PFS rate was observed among women on ribociclib + fulvestrant compared with those on fulvestrant only in the first-line (defined as treatment naïve for advanced breast cancer; median PFS, not reached vs 18.3 months, HR, 0.577, 95 percent CI, 0.415–0.802) and second-line setting (defined as up to one line of prior endocrine therapy for advanced breast cancer; median PFS, 14.6 vs 9.1 months, HR, 0.565, 95 percent CI, 0.428–0.744).
The overall response and clinical benefit rates were also significantly higher among patients who received ribociclib + fulvestrant vs fulvestrant only (32.4 percent vs 21.5 percent; p<0.001 and 70.2 percent vs 62.8 percent; p=0.020, respectively), though these findings are still immature, said the researchers.
The most common non-haematologic all-grade adverse events reported in the ribociclib + fulvestrant vs fulvestrant only groups were nausea, fatigue, and diarrhoea (45.3 percent vs 28.2 percent, 31.5 percent vs 33.2 percent, and 29.0 percent vs 20.3 percent, respectively). Grade 3 and 4 febrile neutropenia only occurred among women in the ribociclib + fulvestrant group (46.6 percent and 6.8 percent, respectively), with no cases reported in the fulvestrant only group.
“The efﬁcacy results seen here for treatment-naïve advanced disease as well as those from other studies of CDK4/6 inhibitors in HR+/HER2- breast cancer supports the study of ribociclib in early HR+/HER2- disease,” said Slamon.
“Additional analyses from the study may help further elucidate mechanisms of resistance to endocrine therapy and CDK4/6 inhibitors,” he added.
*CDK: Cyclin-dependent kinase
**MONALEESA-3: Study of efficacy and safety of LEE011 in men and postmenopausal women with advanced breast cancer***BIRC: Blinded Independent Review Committee