October 11, 2016

Ribociclib Plus Letrozole Improves PFS in Patients With Metastatic HR-Positive Breast Cancer

By Walter Alexander

COPENHAGEN, Denmark -- October 11, 2016 -- Ribociclib plus letrozole was well tolerated and significantly prolonged progression-free survival (PFS), compared with letrozole alone, in postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer who had received no prior therapy.

“Ribociclib with letrozole represents an important advance for patients with metastatic hormone receptor-positive breast cancer,” said Gabriel Hortobagyi, MD, University of Texas M. D. Anderson Cancer Center, Houston, Texas, at the 41st European Society for Medical Oncology (ESMO) Congress.

The finding of benefit, Dr. Hortobagyi said, was consistent across patient subgroups and secondary endpoints.

The phase 3 MONALEESA-2 study included 668 post-menopausal women with HR-positive/HER2-negative metastatic or locally advanced breast cancer with no prior therapy for advanced disease. Patients were randomised to receive ribociclib 600 mg/day (3 weeks on/1 week off) plus letrozole 2.5 mg/day (n = 334) or letrozole plus placebo (n = 334).

The trial was terminated prematurely when at interim analysis it was already apparent that the primary endpoint had been met.

Median PFS had not been met in the ribociclib plus letrozole arm and was 14.7 months in the placebo plus letrozole arm (P = .00000329).

Dr. Hortobagyi underscored that differences between the treatment arms emerged early and were sustained.

While serious adverse events occurred in fewer than 5% of patients in both arms, other adverse events were significantly more common in the ribociclib arm. Neutropenia occurred in 59% of patients in the ribociclib arm compared with 1% of the placebo arm; leukopenia occurred in 21% vs 1%; and lymphopenia in 7% vs. 1%.

Nausea, vomiting, diarrhoea, alopecia, rash, and transaminase elevations were also reported more frequently with the combination than with letrozole alone.

Most adverse events were grade 1/2, and were managed with dose interruptions and reductions. Very few patients discontinued treatment, reported Dr. Hortobagyi.

Patients with measurable disease at baseline had a significantly higher objective response rate to ribociclib plus letrozole compared with letrozole alone (53% vs 37%; P = .00028).

Dr. Hortobagyi said that the results are paradigm changing. “We have not had studies in metastatic breast cancer before with this magnitude of benefit,” he said.

[Presentation title: First-Line Ribociclib + Letrozole for Postmenopausal Women With Hormone Receptor-Positive (HR+), HER2-Negative (HER2-), Advanced Breast Cancer (ABC). Abstract LBA1]

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