Liz Meszaros, MDLinx | September 13, 2017
The addition of abemaciclib—a cyclin-dependent kinase (CDK) 4/6 inhibitor—to endocrine therapy improved progression-free survival (PFS) compared with endocrine therapy alone, as initial therapy in postmenopausal women with hormone receptor positive, HER2 negative advanced breast cancer, according to results from the MONARCH 3 study, which were presented at the European Society for Medical Oncology (ESMO) 2017 Congress.
“This is the third study demonstrating that the combination of endocrine therapy with a CDK4/6 inhibitor is better than endocrine therapy alone,” said lead author Dr. Angelo Di Leo, medical oncologist, Sandro Pitigliani Medical Oncology Department, Hospital of Prato, Istituto Toscano Tumori, Prato, Italy. “Abemaciclib reduced the risk of disease progression by 46%.”
He added: “The data also show we may be able to better distinguish benefit among groups of patients. In patients with more challenging disease characteristics such as liver metastases, patients had substantial benefit from the addition of abemaciclib. However, in the subgroups with bone metastases only, or with an indolent disease, relapsing years after stopping adjuvant endocrine therapy, patients had an excellent prognosis with endocrine therapy alone.”
For this phase 3, randomized, double-blind study, Dr. Di Leo and fellow researchers enrolled 493 patients from 22 countries never treated for metastatic disease. The study’s primary endpoint was PFS.
They presented results from their 18-month interim analysis here at the meeting, reporting that they found that the combination of abemaciclib and endocrine therapy significantly lengthened PFS (HR: 0.543; P=0.000021). In patients with measurable disease, the objective response rate was 59% in the abemaciclib arm, compared with 44% in the placebo arm (P=0.004).
Side effects were greater in the abemaciclib group, including diarrhea (81.3% vs 41.3%, respectively), and neutropenia (29.8% vs 1.9%).
“It is well known that these patients have a better prognosis than those with liver or lung metastases, or who relapse early during the course of adjuvant endocrine therapy. Now for the first time, we have insights suggesting that patients with certain clinical characteristics may benefit differently from treatment with a CDK 4/6 inhibitor, including the possibility that some patients with a good prognosis may be able to start on endocrine therapy alone. In such patients, CDK 4/6 inhibitors could potentially be reserved as a next line of treatment for metastatic disease. This idea warrants further study given our data," said Dr. Di Leo.
"In our study, nearly one-third of patients had bone metastases only or a tumor relapsing several years after stopping adjuvant endocrine therapy," continued Dr. Di Leo. "This is a clinically relevant proportion of patients for whom we may consider delaying use of a CDK 4/6 inhibitor. This may be a more optimal treatment strategy for some patients since it can avoid the toxicity of first line CDK 4/6 inhibitors and save costs," Dr. Di Leo concluded.
“Abemaciclib is the third CDK4/6 inhibitor to be tested in advanced breast cancer and the MONARCH 3 trial confirms the role of this new class of agents in combination with endocrine therapy in the treatment of metastatic breast cancer,” commented Dr. Giuseppe Curigliano, director, Division of New Drug Development, European Institute of Oncology (IEO), University of Milan, Milan, Italy.
“Many patients with metastatic disease still receive chemotherapy, despite guidelines and data from clinical trials. This study confirms that we should avoid chemotherapy in hormone receptor-positive, HER2-negative metastatic breast cancer if visceral crisis is not present,” he added.
“The major question that still needs to be answered is the optimal sequence of treatment in the era of CDK 4/6 inhibitors. Should we use these agents in the first-line setting or is there a space to start with endocrine therapy alone and to add CDK 4/6 inhibitors at progression? An academic driven trial should be designed to address this question,” concluded Dr. Curigliano.