Abemaciclib with fulvestrant effective in advanced breast cancer subtype
CHICAGO — Abemaciclib in combination with fulvestrant demonstrated clinical activity in women with hormone receptor–positive, HER-2–negative advanced breast cancer who progressed on endocrine therapy, according to the results of a MONARCH 2, double blind phase 3 trial presented at the ASCO Annual Meeting.
“The response rate we saw was one of the highest ever recorded in this endocrine resistant population and the change in tumor size was long-lasting,” George W. Sledge, Jr., MD, professor of medicine at the Stanford University Medical Center, said during his presentation.
In a previous study, abemaciclib (LY2835219, Eli Lilly) — an oral CDK4/6 inhibitor — performed well as monotherapy in patients with treatment-refractory hormone receptor–positive metastatic breast cancer when dosed on a continuous schedule. For this study, researchers assessed its tolerability and activity when combined with fulvestrant (Faslodex, AstraZeneca) — a selective ER degrader that targets the function of the hormone receptor without interfering with estrogen levels.
The analysis included 669 women who progressed within 12 months of ending adjuvant endocrine therapy or who were on first-line endocrine therapy and had not received chemotherapy for metastatic disease. Researchers randomly assigned women 2:1 to receive 500 mg fulvestrant with abemaciclib (150 mg every 12 hours or 200 mg prior to amendment; n = 446) or with placebo (n = 223).
Researchers stratified patients by metastatic site (visceral vs. bone only vs. other) and resistance to prior endocrine therapy (primary vs. secondary).
PFS served as the primary endpoint. Secondary endpoints included objective response rate, safety and efficacy.
Most participants (82%) presented as postmenopausal, 72% had measurable disease, 56% had visceral disease and 25% experienced primary endocrine therapy resistance.
In the intent-to-treat population, 379 PFS events occurred. Those treated with abemaciclib and fulvestrant demonstrated a median PFS of 16.4 months, compared with 9.3 months for those who received placebo and fulvestrant (HR = 0.55; 95% CI, –0.44 to 0.68).
Among women with measurable disease, ORR was 48.1% with abemaciclib and fulvestrant and 21.3% with placebo and fulvestrant.
However, women assigned abemaciclib and fulvestrant experienced higher rates of adverse events than the placebo group. Adverse events included diarrhea (86.4% vs. 24.7%), neutropenia (46% vs. 4%), nausea (45.1% vs. 22.9%) and fatigue (39.9% vs. 26.9%).
“Diarrhea occurred early, typically in the first cycle of treatment, though the intensity and frequency of the diarrhea were strongly related to the starting dose,” Sledge said. – by Chuck Gormley
Sledge G, et al. Abstract 1000. Presented at: ASCO Annual Meeting; June 2-6, 2017; Chicago.
Disclosures: Researchers report no relevant financial disclosures.