At the European Society of Medical Oncology (ESMO) 2019 Congress, overall survival results of the phase III MONALEESA-3 trial of postmenopausal patients with hormone receptor-positive, HER2-negative advanced breast cancer treated with fulvestrant (faslodex) plus/minus ribociclib (kisqali) were discussed by leading experts across the globe.
One of these experts was Patrick Neven, MD, PhD
, who spoke on the positive results of the study and what this could mean for caring for patients with breast cancer. Neven, GYN oncologist at University Hospital Leuven, Leuven, Belgium, sat down with OncLive®
, a sister publication to Oncology Nursing News®
, to discuss the rationale and results of ribociclib used in the trial and other highlights from ESMO.
OncLive®: Can you discuss the rationale for the drug?
: So the MONALEESA-3 study is a phase 3 study improve the outcome of patients who have endocrine estrogen receptor-positive stage-4 breast cancer, and the study is trying to improve the progression-free survival and as a secondary endpoint, the overall survival of patients who have first or second-line treatment. The endocrine treatment was given, and this study used fulvestrant (faslodex) and the study randomized 1 to 2 fulvestrant plus placebo versus fulvestrant plus ribociclib. There was also a group of patients with endocrine sensitive breast cancer and a group of patients with endocrine-resistant breast cancer.
What was the key inclusion criteria of the study?
The key inclusion of patients with stage-4 endocrine disease who are endocrine treatment naïve, or who had a maximum one line of endocrine treatment in the advanced setting, or patients who had earlier laps on the adjuvant treatment including patients who relapsed within 12 months of stopping the adjuvant treatment. They were all postmenopausal and had ER-positive HER2 negative stage-4 breast cancer as well.
Can you discuss the efficacy of ribociclib to date?
The efficacy that was reported at ESMO is on the secondary endpoint, which is the overall survival comparing fulvestrant plus placebo versus fulvestrant plus ribociclib. and it shows a clear improvement in the overall survival with about 10 months, which is quite impressive. The median overall survival was not reached in ribociclib group which was 14 months in the placebo group. So, it's quite impressive for overall survival benefits.
CDK46 inhibitors are tolerated fairly well, but were there toxicities of note?
They were tolerated fairly well, but there are some hematologic toxicities. Some patients feel tired, they sometimes have anemia, they feel nauseous. There also might be a bit of hair loss, which can be disturbing. Grade 3 and 4 hematological toxicity was present in more than 10% of the patients, which is sometimes the reason to delay the dose or to reduce the dose.
What are the differences between MONARCH-2 and MONALEESA-3, and how might they impact each other?
In MONARCH-2 one group of patients in endocrine resistance and the other is endocrine sensitive and endocrine-resistant. So, they're quite different. They were both different together with fulvestrant. These are two different trials, but this will, of course, impact the clinical practice that we give to patients in treatment.
The question is, where do we position this in the ideal sequence? And this depends on a lot of variables, like the volume of the tumor length, the endocrine sensitivity, the absence of presence of visceral disease, and the age of the patient. We also have a little survival data in premenopausal patients with MONALEESA-7. So, we will give it either first or in the second line, but this position depends on a lot of variables. If patients have low volume disease, we give mono treatment and we keep the combination in the second line.
What makes the results of the MONALEESA-3 trial impressive?
Beyond the overall survival benefit, it’s the PFS that was seen with the patients who were endocrine sensitive and the patients who were endocrine naïve and we have dual patients who do well for 33 months before they have to change treatments. Also impressive is the delay in starting chemotherapy, which was significantly lower compared to the patients who have to combination with ribociclib as compared to the placebo group.