麻豆传媒

SAN ANTONIO -- A CDK4/6 inhibitor plus endocrine therapy combination extended progression-free survival (PFS) by nearly a year compared with chemotherapy as first-line treatment for premenopausal patients with aggressive, hormone receptor (HR)-positive/HER2-negative advanced breast cancer, a randomized study showed.

In the phase II trial, median PFS reached 24.0 months with ribociclib (Kisqali) plus endocrine therapy versus 12.3 months with physicians' choice of combination chemotherapy (HR 0.54, 95% CI 0.36-0.79, P=0.0007), Yen-Shen Lu, MD, PhD, of the National Taiwan University Hospital in Taipei, reported during a press conference at the San Antonio Breast Cancer Symposium.

More than 50% of patients in the so-called RIGHT Choice study had visceral crisis, defined as the presence of metastases that compromise the function of vital organs.

Time to response was not significantly different between the ribociclib/endocrine therapy and chemotherapy arms (4.9 and 3.2 months, respectively), an important consideration for patients with aggressive breast cancer, and tolerability was superior with the CDK4/6 combination, he said.

The findings therefore are "practice changing," said Lu, given that chemotherapy has been the preferred initial treatment choice for patients with HR-positive/HER2-negative advanced breast cancer with aggressive characteristics such as visceral crisis. Physicians may be hesitant to move away from combination chemotherapy in this population because of the rapid tumor response, he said, but the data from RIGHT Choice endorse the choice of ribociclib plus endocrine therapy, he said.

"When we were discussing this at our abstract committee meeting, we were all really scrutinizing it to see how you selected the patients that have rapidly progressing disease, and we couldn't find anything wrong," said press conference moderator Virginia Kaklamani, MD, from UT Health San Antonio. "Because we didn't believe the results."

"It will change some of that standard of care," she continued. "We don't use a lot of chemotherapy nowadays because of how well the CDK4/6 inhibitors work, but I think the little that we use is probably now dead."

The study included 222 premenopausal or perimenopausal patients with aggressive, HR-positive/HER2-negative advanced breast cancer. Patients were randomly assigned 1:1 to either ribociclib (600 mg daily, 3 weeks on/1 week off) plus an aromatase inhibitor (letrozole or anastrozole) and goserelin or physicians' choice of combination chemotherapy (docetaxel plus capecitabine, paclitaxel plus gemcitabine, or capecitabine plus vinorelbine).

Aggressive disease was defined as the presence of symptomatic visceral metastases, rapid disease progression or impending visceral compromise, or markedly symptomatic nonvisceral disease. Eligible patients could not have received prior systemic therapy for advanced breast cancer.

In addition to a longer median PFS, the median time to treatment failure was also longer among patients treated with ribociclib plus endocrine therapy, at 18.6 months versus 8.5 months among patients treated with combination chemotherapy (HR 0.45, 95% CI 0.32-0.63).

Overall response rates were similar between the two treatment arms, at 65% in the CDK4/6 inhibitor arm compared with 60% in the chemotherapy arm.

Serious, treatment-related adverse events (AEs) occurred in 1.8% of patients receiving ribociclib plus endocrine therapy and in 8% of those receiving combination chemotherapy, and the rates of grade 3/4 treatment-related serious AEs were 0.9% and 7%, respectively. Some 7% of patients treated with ribociclib plus endocrine therapy and 23% treated with combination chemotherapy discontinued at least one component of study treatment due to treatment-related adverse events.