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Verzenio plus Faslodex improved progression-free survival in HR+/HER2– advanced breast cancer after CDK/6i failure, with a manageable safety profile.
Verzenio plus Faslodex significantly improved progression-free survival in HR+/HER2– advanced breast cancer after CDK/6i failure, with manageable side effects.
Among patients with hormone receptor-positive (HR+), HER2-negative (HER2–) advanced breast cancer, Verzenio (abemaciclib) plus Faslodex (fulvestrant) demonstrated significantly improved progression-free survival (PFS) rates following disease progression on cyclin-dependent kinase 4/6 inhibitors (CDK/6i) combined with endocrine therapy (ET), according to study findings published in Journal of Clinical Oncology.
“[This] postMONARCH trial supports maintaining CDK4/6 inhibition with [Verzenio], while switching the ET backbone, after disease recurrence or progression on a CDK4/6i plus ET,” lead study author Dr. Kevin Kalinsky and collogues wrote in the journal. “This combination offers an additional targeted therapy option for patients with HR+, HER2– [advanced breast cancer].”
Kalinsky is a professor and director in the Division of Medical Oncology, Department of Hematology and Medical Oncology, at Emory University School of Medicine, and director of the Glenn Family Breast Center at Winship Cancer Institute, in Atlanta, Georgia.
After a median follow-up of 13 months at the primary analysis (258 events), Verzenio plus Faslodex reduced the risk of progression or death by 27% compared with placebo plus Faslodex, with a median PFS of 6 months versus 5.3 months. The six-month PFS rates were 50% and 37%, respectively.
Progression-free survival (PFS): the length of time during and after treatment that a patient lives with the disease without it worsening.
Objective response rate (ORR): the percentage of patients whose cancer shrinks or disappears after treatment, typically measured by imaging or other diagnostic tools.
These findings were supported by a blinded independent central review, which showed a 45% reduced risk of progression or death. A consistent treatment effect was observed across major clinical and genomic subgroups, including those with or without ESR1 or PIK3CA mutations. Among patients with measurable disease, investigator-assessed objective response rate (ORR) was higher with Verzenio plus Faslodex compared with placebo plus Faslodex (17% versus 7%).
Regarding safety, grade 3 (severe) or worse side effects occurred in 55% and 20% of patients, with diarrhea being the most common event in the Verzenio arm (4% grade 3 or worse). Serious side effects were reported in 24% and 11%, with pneumonia being the most frequent (4% versus 2%).
Dose interruptions due to side effects occurred in 55% versus 7% of patients, mainly from neutropenia (20%), which is a lack of white blood cells. Dose reductions were 30% versus 3%, primarily from diarrhea (9%). Treatment discontinuation due to side effects was 6% versus 0%. Deaths occurred in four (2%) and two (1%) patients, with one pneumonia-related death in the Verzenio arm which was considered treatment-related.
“No new safety signals were identified with [Verzenio plus Faslodex] and the discontinuation rate due to [side effects] was low [6%],” study authors wrote. “Additionally, the grade 3 diarrhea and dose modification rates were lower than in previous studies, likely reflecting increased familiarity with [Verzenio]. Overall, [Verzenio plus Faslodex] had a predictable and manageable toxicity profile.”
This study randomly assigned 368 (mean age, 59 years) patients, with 182 receiving Verzenio plus Faslodex and 186 receiving placebo plus Faslodex. At baseline, 221 of 367 patients (60%) had visceral disease, including 38% with liver metastases, while 20% had bone-only disease.
The primary end goal of the trial was PFS, and the secondary end goals included PFS by blinded independent central review, ORR and safety.
“To our knowledge, the postMONARCH trial is the first randomized, placebo-controlled phase 3 study to demonstrate benefit of continued CDK4/6 inhibition beyond progression on a CDK4/6i,” study authors concluded.
Reference:
“Abemaciclib Plus Fulvestrant in Advanced Breast Cancer After Progression of CDK4/6 Inhibition: Results From the Phase 3 postMONARCH Trial,” by Dr. Kevin Kalinsky, et al., Journal of Clinical Oncology.
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