Practice Update: Oncology

CONFERENCE COVERAGE 20

MONARCH 3: Abemaciclib Improves Progression-Free Survival in Endocrine-Sensitive Advanced Breast Cancer Although most women benefited substantially from the addition of the cyclin-dependent kinase (CDK) 4/6 inhibitor abemaciclib as initial treatment for endocrine-sensitive advanced breast cancer, with extended progression-free survival, approximately one-third of women may not need a CDK 4/6 inhibitor as initial treatment. The findings from the 18-month interim analysis of the phase III, randomized, double-blind MONARCH 3 trial of abemaciclib vs placebo were reported at the European Society for Medical Oncology (ESMO) 2017 Congress, from September 8–12.

I n MONARCH 3, led by Angelo Di Leo, MD, PhD, of the Hospital of Prato, Isti- tuto Toscano Tumori, Italy, abemaciclib or placebo was added to endocrine ther- apy with a nonsteroidal aromatase inhibitor (anastrozole or letrozole) as initial therapy in postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. A total of 493 patients from 22 countries who had never been treated for metastatic disease were included in the analysis. Compared with single-agent endocrine therapy alone, the addition of abemaciclib significantly increased the primary end- point of progression-free survival (hazard ratio 0.543 [P = .000021]). In patients with measurable disease, the objective response rate was 59% with abemaciclib vs. 44% in with placebo (P = .004). The most common adverse events were diarrhea and neutropenia, which occurred in 81.3% and 41.3%, respectively with abemaciclib vs. 29.8% and 1.9% with placebo. In a written release from ESMO, Dr. Di Leo noted that MONARCH 3 is the third study to demonstrate that the combination of endocrine therapy with a CDK4/6 inhibi- tor is better than endocrine therapy alone, with abemaciclib reducing the risk of dis- ease progression by 46%. He added that the data also showed that it may be possible to better distinguish ben- efits among groups of patients. In patients with more challenging disease character- istics, such as liver metastases, patients benefited substantially from the addition of abemaciclib. By contrast, in subgroups with bone metastases only or with indolent disease that relapsed years after stopping adjuvant endocrine therapy, endocrine therapy alone conferred an excellent prognosis. According to Dr. Di Leo, for the first time, data suggest that patients with certain clin- ical characteristics may benefit differently from treatment with a CDK 4/6 inhibitor. Some patients with a good prognosis

may be able to receive endocrine ther- apy alone, and CDK 4/6 inhibitors could be reserved as a next line of treatment for metastatic disease, an idea that warrants further investigation. Nearly one-third of patients had bone metastases only or a tumor that relapsed several years after stopping adjuvant endo- crine therapy. Dr. Di Leo pointed out that this is a clinically relevant proportion of patients, and in these patients, the use of a CDK 4/6 inhibitor could be delayed, which would minimize costs and decrease toxicity. Giuseppe Curigliano, MD, of the Euro- pean Institute of Oncology, University of Milan, Italy, stated in the written release that abemaciclib is the third CDK 4/6 inhibitor to

be evaluated in advanced breast cancer. MONARCH 3 confirms the role of this new class of agents in combination with endo- crine therapy for metastatic breast cancer. He added that many patients with meta- static disease still receive chemotherapy, despite guidelines and data from clinical trials. The interim results from this study suggest that chemotherapy should be avoided in hormone receptor-positive, HER2-negative metastatic breast cancer in the absence of visceral crisis. Dr. Curigliano suggested that an academ- ic-driven trial should address questions about the optimal sequencing of endocrine therapy and CDK 4/6 inhibitors. www.practiceupdate.com/c/58121

PRACTICEUPDATE ONCOLOGY