Ribociclib Plus ET Yields 46% Reduction in Disease Progression in Pre/Perimenopausal HR+/HR- Advanced Breast Cancer

The first-line combination of ribociclib (Kisqali) and endocrine therapy (ET) may represent a new standard of care treatment option for pre/perimenopausal patients with aggressive hormone-receptor (HR)-positive and HER2-negative advanced breast cancer, according to Yen-Shen Lu, MD, PhD.

Lu’s statement is based on findings from the randomized, phase 2, open label, multicenter RIGHT Choice trial (NCT03839823), for which he presented results of at a press briefing held during the San Antonio Breast Cancer Symposium 2022.

Ribociclib in combination with letrozole or anastrozole plus goserelin achieved a 46% relative reduction in the risk of disease progression or death, showing a statistically significant improvement in progression-free survival (PFS) compared with combination chemotherapy, in the study. These chemotherapy combinations consisted of either docetaxel plus capecitabine, paclitaxel plus gemcitabine, or capecitabine plus vinorelbine.

“Chemotherapy is a conventionally a treatment option for patients with aggressive advanced breast cancer who urgently need a treatment with high response rate, in cases where tolerability is not a concern,” explained Lu, oncologist at the National Taiwan University Hospital in Taipei, Taiwan, in explanation of the control arm.

Lu also explained that 3 previous phase 3 trials of ribociclib as treatment of patients with advanced breast cancer showed consistent PFS and overall survival (OS) benefit.

RIGHT Choice included 222 pre/perimenopausal patients with HR-positive/HER2-negative advanced breast cancer who had aggressive disease, visceral metastases, rapid disease progression of visceral compromise, and considerably symptomatic non-visceral disease. All patients who were included did not have prior systemic treatment for advanced breast cancer and had measurable disease.

Patients in the study were randomized 1:1 to receive 600 mg of ribociclib administered for 3 weeks on and 1 week off in combination with standard dose of ET or the control of combination chemotherapy. In addition to the primary end point of PFS, patients were assessed for secondary end points including time to treatment failure, objective response rate (ORR), clinical benefit rate, OS, safety, and quality of life.

At baseline, the characteristics were well-balanced between the 2 treatment arms. Most patients above the age of 40, and more than half, were Asian in both arms. Notably, 84.8% of patients in the ribociclib plus ET arm vs 86.4% in the combination chemotherapy arm had ≥ 50 endocrine receptor (ER) positivity. In terms of aggressive disease characteristics in the experimental vs control arm were rapid progression (20.5% v 16.4%), symptomatic non-visceral disease (13.4% v 14.5%), symptomatic visceral metastases (66.1% v 69.1%), and visceral crisis (54.5% v 50.0%).

At the time of data cutoff, treatment with ribociclib plus ET was ongoing in 46% of patients compared with 24% in the combination chemotherapy arm.

At a median follow-up of 24.1 months, the median PFS observed with ribociclib and ET was 24.0 months vs 12.3 months with combination chemotherapy (95% CI; HR, 0.54, 0.36-0.79; P = .0007). The PFS benefit of ribociclib, and ET was also consistent in most patient subgroups.

The ribociclib combination also showed improvement in ORR in comparison with combination chemotherapy. The ORR was 65.5% with ribociclib and ET vs 60.0% with combination chemotherapy, however, the time to response in the ribociclib/ET arm was consistent with combination chemotherapy at 4.9 months vs 3.2 months (95% CI, HR, 0.78, 0.56-1.09).

The combination of ribociclib and ET was associated with less toxicity than combination chemotherapy. Of the 212 patients evaluated for safety, the treatment-related serious adverse events (AEs) occurred in 1.8% of the ribociclib/Et arm vs 8.0% of the control arm, and these AEs were grade 3/4 in 0.9% vs 7.0%, respectively. Any-grade treatment-related AEs led to discontinuation in 7.1% of the ribociclib combination arm vs 23.0% of the chemotherapy combination arm, and grade 3/4 treatment-related AEs led to discontinuation in 6.3% vs 7.0%, respectively.

The most common symptomatic AEs in the ribociclib/ET arm vs the combination chemotherapy arm were nausea (12.0% v 27.0%), vomiting (7.1% v 30.0%), and (2.7% v 26.0%).

“The curve we provide is in line with the clinical experience, and if you look at the disease progression in the first few months, they are identical between the chemotherapy combination versus ribociclib. With that kind of curve, especially with the high response rate we demonstrated, this result will tell the doctors that treatment with ribociclib should be safe,” Lu said in response to a question from Targeted Oncology™ at the press briefing.

_REFERENCES:

_{Mahidin E, Azim H, and ERALP Y, et al. GS1-10 Primary results from the randomized Phase II RIGHT Choice trial of premenopausal patients with aggressive HR+/HER2− advanced breast cancer treated with ribociclib + endocrine therapy vs physician’s choice combination chemotherapy. Presented at: San Antonio Breast Cancer Symposium 2022; December 6–10, 2022. San Antonio, TX. Abstract GS1-10.}