Frontline Ribociclib/Endocrine Therapy Generates Similar ORR to Combination Chemo in HR+/HER2– Advanced Breast Cancer

Ribociclib (Kisqali) plus endocrine therapy produced similar responses to physician’s choice of combination chemotherapy in premenopausal/perimenopausal patients with aggressive hormone receptor–positive/HER2-negative advanced breast cancer. The combination could represent a viable option in the frontline setting, particularly for those who are contraindicated for combination chemotherapy, according to Yen-Shen Lu, MD, PhD.

Data from the phase 2 RIGHT Choice trial (NCT03839823) presented at the 2022 San Antonio Breast Cancer Symposium showed ribociclib plus endocrine therapy demonstrated a median progression-free survival (PFS) of 24.0 months compared with 12.3 months for combination chemotherapy (HR, 0.54; 95% CI 0.36-0.79; P = .0007). Additionally, the overall response rate (ORR) was 65.2% in the ribociclib arm vs 60.0% in the chemotherapy arm.

“For the patients who are intolerable to combination chemotherapy, ribociclib plus endocrine therapy has a greater response rate than single-agent chemotherapy. For [other] patients, [even if] they are tolerable to combination chemotherapy, ribociclib plus endocrine therapy can provide a longer PFS, lower toxicity, and better treatment compliance, which is important for the success of treatment for our patients,” Lu said.

In an interview with OncLive®, Lu discussed the primary results of the RIGHT Choice trial and what they could mean for the use of ribociclib and endocrine therapy in this population. He is an oncologist in the Department of Oncology at National Taiwan University Hospital in Taipei, Taiwan.

OncLive®: What was the target patient population for the RIGHT Choice trial investigating ribociclib and endocrine therapy vs physician’s choice of combination chemotherapy?

Lu: RIGHT Choice was a randomized phase 2 study to compare the efficacy of ribociclib plus endocrine therapy vs combination chemotherapy in a hard-to-treat population: patients with aggressive, hormone receptor–positive/HER2-negative advanced breast cancer. We specifically chose premenopausal and perimenopausal women because they are more tolerable to the toxicity associated [with] combination chemotherapy.

If a physician considered that combination chemotherapy would be the treatment of choice [for an individual patient], then she would be eligible [for the trial]. Inclusion criteria included symptomatic visceral metastases, rapid disease progression, or markedly symptomatic non-visceral disease. If [a patient met] 1 of the 3 [criteria] points, then a physician may consider that combination chemotherapy would be the treatment of choice for [one of these patients].

Patients were [randomly assigned] to receive ribociclib plus non-steroidal aromatase inhibitor with goserelin or physician’s choice of combination chemotherapy, which included docetaxel plus capecitabine, paclitaxel plus gemcitabine, or capecitabine plus vinorelbine.

The primary end point was PFS, and [exploration of] a lot of key secondary end points was planned.

What were the key efficacy data presented at the 2022 SABCS?

For the primary end point of PFS, the results showed that first-line ribociclib plus endocrine therapy provided a significant PFS benefit of [more than] 1 year [vs] combination chemotherapy [HR, 0.54; P = .0007]. The benefit of ribociclib plus endocrine therapy over combination chemotherapy was significant and clinically meaningful.

Regarding the secondary end points, including ORR and time to response, they were similar between combination chemotherapy and ribociclib plus endocrine therapy.

We all know for combination chemotherapy, it has a high tumor response rate, which is why it is preferred for patients with aggressive disease. With our study, we showed that ribociclib plus endocrine therapy met [a similar] high tumor response rate. [These] data [provide] more confidence to use [ribociclib plus endocrine therapy] and reluctance to use combination chemotherapy because it is associated with more toxicity. That is our key result.

What safety signals did investigators observe in each arm?

Neutropenia and leukopenia were higher in the ribociclib [arm] , but everybody knows that CDK4/6 inhibitor–related neutropenia is asymptomatic, and it is rare to have infection. On the other hand, the incidence of symptomatic adverse effects [AEs], such as nausea, vomiting, diarrhea, alopecia, and hand-foot syndrome, were much higher in patients being treated with combination chemotherapy. Patients will experience more symptomatic AEs if they receive combination chemotherapy [vs] ribociclib [plus endocrine therapy].

What unmet needs could ribociclib plus endocrine therapy address in the first line setting for patients with aggressive hormone receptor–positive/HER2-negative advanced breast cancer?

Combination chemotherapy is one of the standards of care, and for a patient who is relatively intolerable to combination chemotherapy, then all you can [use] is a single-agent chemotherapy. [However], for a patient with a critical situation, you need a regimen with high response rates. Therefore, patients have to tolerate AEs.

What future opportunities could this trial create for ribociclib in this indication?

People [could] start to use ribociclib plus endocrine therapy as a first-line treatment and consider if there is any critical need to differentiate patients who may need a more aggressive treatment vs those who do not. Just using ribociclib [plus endocrine therapy] will be good enough.

These results showed the simple conclusion that [for] the vast majority of the patients, frontline treatment choice could be ribociclib plus endocrine therapy. You don't have to worry about how to assess the patient's condition, disease status, or tumor status. That will make the data much easier to apply to treat our patients.

What other recommendations would you share for the use of ribociclib plus endocrine therapy in this patient population?

I would like to remind [colleagues] that according to the [5th ESO-ESMO international consensus guidelines for advanced breast cancer], they raised the bar to define visceral crisis. If a patient has a liver metastasis, then they have to have a bilirubin level greater than 1.5 times the upper limit of normal. [However], this is not included in this clinical trial because dose modification was difficult in either the chemotherapy arm or the ribociclib arm. That's why we did not recruit this population. When you try to treat the disease population, a close monitoring plan for toxicity and efficacy will be mandatory [if patients] receive either receive chemotherapy or ribociclib.

Reference

Lu Y-S, Mahidin EIBM, Azim H, et al. 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 physicians choice combination chemotherapy. Presented at: 2022 San Antonio Breast Cancer Symposium; December 6-10, 2022; San Antonio, TX. Abstract GS1-10.