RIBECCA Trial Confirms Role of Ribociclib Combination in HR+ HER2-Negative Breast Cancer

Andreas Hartkopf, MD

Andreas Hartkopf, MD

In recent years, the role of ribociclib in hormone receptor (HR)-positive HER2-negative advanced breast cancer has been investigated in phase III clinical trial, as monotherapy or in combination with other drugs like letrozole (Femara, NCT01958021) and fulvestrant (NCT02422615).

RIBECCA is an open-label multicenter phase IIIb clinical trial which was conducted in Germany to further validate the findings of the phase III MONALEESA-2 trial, which demonstrated positive findings in terms of progression-free survival (PFS) for ribociclib (Kisqali) as treatment of patients with postmenopausal HR-positive HER2-negative advanced breast cancer.

Interim data from the RIBECCA study were presented at the San Antonio Breast Cancer Symposium (SABCS) in December 2019. In this trial, however, investigators used the eligibility criteria of MONALEESA-2 for cohort A, while cohort B also included premenopausal women, as well as those who had received prior therapy with either endocrine therapy or chemotherapy.

Over 500 patients were included in the study, and the findings demonstrated no new safety signals. The regimen appeared well tolerated in all patients on the study. RIBECCA confirms validates the findings from MONALEESA-2, but further analysis from the full patient population will be presented in the future, as well as findings from a quality of life analysis.

In an interview withTargeted Oncology,Andreas Hartkopf, MD, Department of Obstetrics and Gynecology, University Hospital Tuebingen, Tuebingen, Germany, discussed the findings from the RIBECCA trial and the key takeaways from these data for patients with HR-positive HER2-negative breast cancer.

TARGETED ONCOLOGY: Could you provide an overview to the RIBECCA trial?

Hartkopf:TheRIBECCAtrialwas conducted in Germany. It is a single-arm trial, and we included patients with HR-positive HER2-negative advanced and metastatic breast cancer. We wanted to investigate this population in addition to the MONALEESA2 population. We included not only patients that were in the first-line but also patients that had received 1 or 2 lines of prior endocrine therapy or chemotherapy for advanced disease.

TARGETED ONCOLOGY: What did you find in this study?

Hartkopf:We divided our population into 2 cohorts, where 70% of the patients were in cohort A which resembled the MONALEESA2 population and 30% of the patients were in cohort B, which included patients who had received additional lines of endocrine therapy or chemotherapy. We also included patients who were premenopausal in cohort B. This was the interim analysis of RIBECCA that was presented at the SABCS.

We saw no new safety signals. The most common adverse event was neutropenia, which we caught in about 60% of patients. The primary objective was to look at the clinical benefit rate, and that was about 75% in cohort A and 65% in cohort B. The PFS data was the same as we have already seen in MONALEESA2. It was about 25 months in cohort A and 9 months in cohort B.

TARGETED ONCOLOGY: How are these data expected to impact the field of breast cancer?

Hartkopf:It is always important to validate data from clinical trials in additional trials to more reflect the clinical situation and the way we prescribe ribociclib in Germany. The data we saw in MONALEESA2 were confirmed, and it confirmed our standard, which is treating HR-positive, HER2-negative patients with CDK4/6 inhibitors.

TARGETED ONCOLOGY: What is important to take home from these data?

Hartkopf:The key takeaway is that CDK4/6 inhibitors are well tolerated. We will present quality of life data later on, but as we saw from the safety analysis, we had no new safety signals, and it is a well-tolerated therapy. For me, this is the standard for treating HR-positive HER2-negative patients.

What is important is that there were so very few patients who had a dose reduction. Most patients stayed on the initial dose. However, this might have been because of 1 factor included in the protocol, which was if a patient had to go off therapy for more than 21 days, the study was terminated for that patient. That may be a reason why we saw not that many dose reductions. My feeling is that dose reductions were only 5%, and this is a little bit lower than I have seen in my clinical experience.

TARGETED ONCOLOGY: Do you have any next steps planned outside of a quality of life analysis?

Hartkopf:This was an interim analysis, so we will have our final analysis, which will be 6 months after the last patient was included. I am looking forward to the quality of life data, which is very important for not only the efficacy but also how patients feel and live with treatment.

TARGETED ONCOLOGY: What are the challenges of treating patients with ribociclib?

Hartkopf:There are challenges concerning treatment, which is that you have to monitor blood values regularly and stay in contact with the patient. For us, it can be a little bit challenging in that we have to measure blood values every 4 weeks at the beginning of therapy.

Another challenge is what to do when a patient progresses under CDK4/6 inhibition. We don’t have real data at the moment for the therapies that we can do after this. What we do is we switch to endocrine therapy or everolimus (Afinitor). We have can use alpelisib (Piqray), which is expected to be approved in a few months in the middle of 2020. We also have the ability to use chemotherapy, but nobody actually knows now what the best post-progression treatment for these patients is.

TARGETED ONCOLOGY: Are there factors you use to determine what patients should receive ribociclib?

Hartkopf: