FDA Approves Faslodex/Abemaciclib for HR+/HER2- Breast Cancer

Peter A. Kaufman, MD

The FDA has approved fulvestrant (Faslodex) for use in combination with the CDK4/6 inhibitor abemaciclib (Verzenio) to treat patients with HR+/HER2- advanced or metastatic breast cancer who have progressed after endocrine therapy.

The combination was previously approved under abemaciclib's label in September. Both approvals were based on phase III results from the MONARCH 2 trial. In 669 women with HR+/HER2- advanced breast cancer, the combination was associated with a statistically significant 7.1-month increase in median progression-free survival (PFS) compared with placebo (16.4 vs 9.3 months; hazard ratio [HR], 0.553; 95% CI, 0.449-0.681; P <.0001).

“This new indication for Faslodex offers another treatment option for women living with HR+, HER2- advanced or metastatic breast cancer with disease progression after endocrine therapy. The study supporting this indication demonstrated that Faslodex used in combination with abemaciclib significantly improves progression-free survival compared to Faslodex and placebo,” Peter A. Kaufman, MD, Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center, said in a statement.

In MONARCH 2, women were randomly assigned to 500 mg of fulvestrant and 150 mg of abemaciclib (n = 446) or fulvestrant plus placebo (n = 223) from August 2014 to December 2015. Eligible patients had progressed during neoadjuvant or adjuvant endocrine therapy, within 12 months of adjuvant endocrine therapy, or during frontline endocrine treatment for metastatic disease. Women were excluded from enrollment if they received chemotherapy, or more than 1 endocrine therapy in the metastatic setting.

Pre/perimenopausal in the trial received the GnRH agonist goserelin acetate beginning at least 4 weeks prior to initiation and continuing throughout the study. Patients remained on treatment until development of progressive disease or unmanageable toxicity.

Median age was 60 years and 56% of patients were white. All patients had an ECOG performance status of 0 or 1.

The overall response rate (ORR) was 35.2% (95% CI, 30.8-39.6) in the experimental arm versus 16.1% (95% CI, 11.3-21.0) in the control arm (P <.001). Investigators observed 14 (3.1%) complete responses in the combination arm compared with 1 (0.4%) in the control arm.

More than two-thirds of patients in both groups had a duration of response lasting 12 months. The median duration of response had not been reached in the combination arm, with 90 responders (57.3%) continuing to receive treatment at the time of the analysis.

Patients with measurable disease had an ORR of 48.1% (95% CI, 42.6-53.6) with the combination compared with 21.3% (95% CI, 15.1-27.6) with placebo (P < .001).

After 12 cycles of treatment, the mean change in tumor size was −62.5% in the experimental arm compared with −32.8% for placebo. The clinical benefit rate favored the combination, 72.2% (95% CI, 68.0-76.4) versus 56.1% (95% CI, 49.5-62.6; P < .001).

The most common any-grade adverse events (AEs) were diarrhea, neutropenia, nausea, fatigue, and abdominal pain. Patients in the combination arm were more likely to develop infection (42.6% vs 24.7%), but investigators said most infections were grade 1 or 2.

Investigators observed serious adverse events (SAEs) in 22.4% of patients in the combination arm and 10.8% of patients in the placebo arm. SAEs possibly related to the study drug were more common in the combination arm, 8.8% versus 1.3%.

Across the study, 24 patients died while receiving therapy or within 30 days of treatment discontinuation, 14 in the abemaciclib arm and 10 in the control arm. Three of the deaths—2 cases of sepsis and 1 case of viral pneumonia, all in the combination arm—were related to the study treatment.

The FDA approved single-agent fulvestrant in August 2017 for postmenopausal women with HR+/HER2- advanced breast cancer who have not received previous endocrine therapy. The drug had previously been approved as a single agent for HR+ patients following progression on endocrine therapy, and in combination with palbociclib (Ibrance) for the treatment of women with HR+/HER2-negative advanced or metastatic breast cancer who progressed following endocrine therapy.

Sledge GW, Toi M, Neven P, et al. MONARCH 2: Abemaciclib in combination with fulvestrant in women with HR+/HER2− advanced breast cancer who had progressed while receiving endocrine therapy. J Clin Oncol. 35:2875-2884.