Sibylle Loibl, MD

Chair of the German Breast Group, Sibylle Loibl, MD, of the University of Frankfurt, commented as a formal discussant of MONALEESA-3 and MONARCH 2. “It’s great to see overall survival in the first- and second-line metastatic breast cancer settings. We haven’t seen that in many years,” she said.

Nadia Harbeck, MD, PhD, of the Ludwig Maximilian University in Munich, called MONALEESA-3 and MONARCH 2 “game changers” in the treatment of hormone receptor–positive HER2-negative advanced breast cancer.

Nadia Harbeck, MD, PhD

At a press briefing, Dr. Harbeck pointed out that MONARCH 2 showed, for the first time, a significant overall survival advantage in a cohort of both pre- and postmenopausal patients. “It’s also the first time we’ve seen overall survival data for abemaciclib, and the delta of 10 months is really clinically meaningful,” she said. “In MONALEESA-3, we have yet to see the median because patients are doing so well.”

For patients with metastatic disease, Dr. Harbeck added, being progression-free for 46 months and avoiding chemotherapy for about 50 months are extremely meaningful outcomes.

Front-line use of cyclin-dependent kinase 4 and 6 inhibitors is now clearly warranted, she suggested. “We should give the best drugs first. You can never be sure a patient will receive second-line treatment.”

Trials Cannot Be Directly Compared

Dr. Loibl devoted a good portion of her formal discussion to describing the features of and differences between the individual trials. Primarily, their populations are different in the extent of pretreatment (and lack thereof), menopausal status, relapse profile, and definitions of endocrine resistance, for example. Their “special characteristics” are sufficient enough to discourage comparisons of their results, she emphasized. “These patient populations are significantly different; therefore, we cannot and should not compare the individual data.”

Differences aside, Dr. Loibl applauded the findings of these trials: Significant improvements in progression-free survival, in both the first and second lines, have now translated into overall survival improvements. “Outcomes improve irrespective of pretreatment, menopausal status, endocrine sensitivity, and site of metastasis. That’s good for our patients,” she said. 

DISCLOSURE: Dr. Loibl has received honoraria from Prime and Chugai and numerous institutional research grants. Dr. Harbeck disclosed relevant relationships with AstraZeneca, Lilly, Novartis, and Pfizer.