News >

Continuous Low-Dose Ribociclib Both Safe and Active in Advanced Breast Cancer

Wayne Kuznar
Published: Friday, Dec 16, 2016

Sara Tolaney, MD, MPH

Sara Tolaney, MD, MPH

A continuous low-dose of ribociclib demonstrated both preliminary activity and an acceptable safety profile when compared with an intermittent dose of ribociclib when combined with fulvestrant in the treatment of postmenopausal patients with hormone receptor (HR)-positive, HER2-negative advanced breast cancer. The results of this phase Ib study were presented at the 2016 San Antonio Breast Cancer Symposium.

Patients in the doublet arm were treated with once-daily ribociclib at either 600 mg/day on a 3-weeks on/1-week off schedule (arm A) or 400 mg/day continuous (arm B) plus fulvestrant, 500 mg/day on day 1 and day 15 of cycle 1/day 1 of subsequent cycles.

Included in the study were postmenopausal women with HR-positive, HER2-negative metastatic or locally advanced breast cancer, whose disease progressed either during or within 12 months of prior adjuvant aromatase inhibitor (AI) therapy or during or within 1 month of AI therapy for metastatic disease. Patients were allowed to receive up to 2 prior lines of chemotherapy for advanced disease, and any number of lines of prior endocrine therapy. Patients with significant cardiac disease or impaired cardiac function were excluded.

Twenty-eight patients, 13 in arm A and 15 in arm B, comprised the doublet arm as of September 12, 2016. Their mean age was 59 years. Patients had received a median of 4 prior antineoplastic therapies. In the metastatic setting, 42.9% received prior chemotherapy (61.5% in arm A vs 26.7% in arm B), 92.9% received prior endocrine therapy, 38.6% received prior PI3K/mTOR inhibitor therapy (23.1% in arm A vs 33.3% in arm B). At the data cut-off, 78.6% of patients discontinued treatment (100% in arm A vs 60.0% in arm B). The most common reason for discontinuation was progressive disease (84.6%).

The most common adverse events (AEs) thought to be study drug-related were neutropenia (64.3%), fatigue (42.9%), and nausea (42.9%), and the most common grade 3/4 AEs thought to be study drug-related were neutropenia (46.4%) and a decrease in white blood cell count (10.7%). Grade 3/4 neutropenia occurred in 61.5% of the intermittent arm, compared with 33.3% of the continuous dosing arm, and the rates of grade 3/4 fatigue were 15.4% and 0%, respectively.

Out of the patients on the intermittent schedule (arm A), 23.1% had a confirmed PR, 69.2% had SD, and 7.7% with non-measureable disease had neither complete response nor progressive disease. The best overall responses in the 7 patients who had received prior fulvestrant were a confirmed PR in 2 patients and SD in 5 patients.

In the continuous ribociclib arm (arm B), 13.3% had a confirmed PR, 46.7% had SD, and 6.7% had progressive disease. The best overall responses in the 6 patients who had received prior fulvestrant were a confirmed PR in 1, SD in 3, non-measureable disease with neither complete response nor progressive disease in 1, and progressive disease in 1.

Next-generation sequencing analysis was performed on tumor samples form 16 patients (7 in arm A and 9 in arm B). Alterations in PI3K3CA were present in 11 patients; of these, 1 had a PR, 7 had SD, and 3 experienced non-measureable disease with neither complete response nor progressive disease. Two patients with alterations in both CCND1 and PIK3CA experienced a SD and non-measureable disease, with neither complete response nor progressive disease.

“To see responses in patients who’ve had prior fulvestrant and have had up to 2 lines of chemotherapy is good,” said Tolaney. “Ribociclib seems active regardless of the presence of PI3K mutation. There is maybe a hint that those who have Cyclin-D amplification may have prolonged durability, at least SD, but the numbers here are very small, and you can’t conclude much from this. It’s more exploratory.”
Tolaney SM, Forero-Torres A, Boni V, et al. Ribociclib + fulvestrant in postmenopausal women with HR+, HER2- advanced breast cancer (ABC). Presented at 2016 San Antonio Breast Cancer Symposium; December 6-10, 2016; San Antonio, TX. Abstract P4 22-12.

... to read the full story
To Read the Full Story

View Conference Coverage
Online CME Activities
TitleExpiration DateCME Credits
Community Practice Connections™: How Do We Leverage PARP Inhibition Strategies in the Contemporary Treatment of Breast Cancer?May 31, 20191.5
Community Practice Connections™: A Better Way to Stop Pain: Paths Toward Responsible Postsurgical Pain Management for Patients With Breast CancerMay 31, 20191.5
Publication Bottom Border
Border Publication
External Resources

MJH Associates
American Journal of Managed Care
MD Magazine
Oncology Nursing News
Pharmacy Times
Physicians' Education Resource
Physician's Money Digest
Specialty Pharmacy Times
OncLive Resources

Conference Coverage
OncLive TV
Peer Exchange
Web Exclusives

About Us
Advisory Board
Contact Us
Forgot Password
Press Releases
Privacy Policy
Terms & Conditions
Intellisphere, LLC
2 Clarke Drive
Suite 100
Cranbury, NJ 08512
P: 609-716-7777
F: 609-939-0221

Copyright OncLive 2006-2018
Intellisphere, LLC. All Rights Reserved.