Press conference moderator Carlos L. Arteaga, MD, said: “This drug is not necessarily the same as palbociclib [Ibrance] or ribociclib. There are subtle differences among these three [cyclin-dependent kinase (CDK) 4/6] inhibitors. The tissue analysis provides us with an enormous opportunity to identify mechanisms of anticancer activity and discover biomarkers and mechanisms associated with drug resistance. It is much harder to do these discovery-focused studies like this in metastatic breast cancer,” he admitted. Dr. Arteaga is the Donna S. Hall Chair in Breast Cancer Research and Director of the Center for Cancer Targeted Therapies at the Vanderbilt-Ingram Cancer Center, Nashville.
The data look great for the CDK4/6 inhibitors, but no one has identified a predictor for response and resistance thus far. We are still unable to shed real light on why patients respond and why resistance develops.— Leif Ellisen, MD, PhD
“Neoadjuvant trials are used to get signals of activity, such as Ki67 at 14 days or objective response at 14 weeks, which can in turn inform progressing or not to adjuvant trials,” he continued.
“The study of mechanisms of resistance will tell us which patients won’t benefit from abemaciclib. This study is not a green light for using this drug in clinical practice. More studies of CDK4/6 agents are ongoing, and they will likely be positive. I wouldn’t be surprised if we eventually have three U.S. Food and Drug Administration–approved CDK4/6 inhibitors, and that would be good news for patients” Dr. Arteaga said.
Commenting on this trial, Leif Ellisen, MD, PhD, Director of the Breast Oncology Program at Massachusetts General Hospital Cancer Center in Boston, said: “The data look great for the CDK4/6 inhibitors, but no one has identified a predictor for response and resistance thus far. We are still unable to shed real light on why patients respond and why resistance develops. We need to figure out biochemical markers for this. The big question will be how to sequence CDK4/6 inhibitors and [phosphoinositide 3-kinase] inhibitors.”
Tufia Haddad, MD, a medical oncologist at Mayo Clinic, Rochester, Minnesota, said the study met its primary endpoint, and now the combination should be studied in the adjuvant setting. “Using loperamide lowered the rates of severe diarrhea that have been associated with abemaciclib. This makes a night-and-day difference in tolerability,” she noted.
Using loperamide lowered the rates of severe diarrhea that have been associated with abemaciclib. This makes a night-and-day difference in tolerability.— Tufia Haddad, MD
“We already have good adjuvant therapy for estrogen receptor–positive breast cancer. Adding a CDK4/6 inhibitor may be an improvement. Patients with operable breast cancer have good outcomes with endocrine therapy, but for those with locally advanced disease at higher risk of relapse, late relapses may occur. In fact, approximately half of relapses occur after 5 years. We must and can do better for these patients, and this is a fertile area of study.” We can do better for these patients, and this is a fertile area of study,” Dr. Haddad predicted.
She mentioned the large, international PALLAS study, with a planned enrollment of 4,600 pre- and postmenopausal women with stages II and III estrogen receptor–positive cancer. They will be treated with physician’s choice of endocrine therapy for 5 years plus or minus palbociclib for 2 years. ■
Disclosure: Drs. Arteaga, Ellisen, and Haddad reported no potential conflicts of interest.
As neoadjuvant therapy, abemaciclib alone or in combination with anastrozole achieved strong signals of anticancer activity in postmenopausal patients with hormone receptor–positive, HER2-negative breast cancer in the neoMONARCH phase II study.1 Abemaciclib alone or in combination with anastrozole...