Breast cancer

Study supports CDK4/6i + endocrine therapy in aggressive advanced breast cancer

First-line ribociclib plus endocrine therapy may be more effective and better tolerated than combination chemotherapy in patients with advanced breast cancer with aggressive disease features, a study has shown

Results from the phase II RIGHT Choice trial presented at SABCS 2022 meeting showed that a combination of CDK4/6 inhibitor and endocrine therapy provided more durable antitumor efficacy with better tolerability and compliance than chemotherapy in pre- or perimenopausal patients with hormone receptor-positive, HER2-negative tumours.

Study investigator Professor Yen-Shen Lu, of the National Taiwan University Hospital, said combination chemotherapy remained the guideline-recommended standard of care for selected patients with advanced breast cancer with aggressive disease features, but these patients are often excluded from clinical trials, meaning there was little evidence on new treatment regimens for them.

“Treatment approaches for patients with visceral crises can sometimes be difficult for clinicians, as there is no precise guidance on treatment strategy,” he told the meeting.

His team therefore designed a head-to-head comparison study, enrolling 222 patients with HR+/HER2− advanced breast cancer (>10% ER+) and no prior systemic therapy. The patients were judged to have aggressive features such as  symptomatic visceral metastases, rapid progression of disease or impending visceral compromise, or markedly symptomatic non-visceral disease.

Participants were randomly assigned to receive ribociclib plus an aromatase inhibitor—letrozole or anastrozole—and goserelin. The other 110 patients were assigned to receive a physicians’-choice combination chemotherapy regimen.

Results presented at SABC 2022 showed that patients treated with ribociclib plus endocrine therapy had a progression-free survival of 24 months, nearly one year more than that of patients treated with chemotherapy (12.3 months). The median time to treatment failure was also longer among patients treated with ribociclib plus endocrine therapy —18.6 months versus 8.5 months among patients treated with chemotherapy.

The overall response rate was similar between the two treatment arms (65.2% for ribociclib plus endocrine therapy and 60% for chemotherapy).

However, the rates of symptomatic adverse events, such as diarrhoea and fatigue, were different: Serious, treatment-related adverse events emerged in 1.8% of patients receiving ribociclib plus endocrine therapy and in 8% of patients receiving combination chemotherapy.

Similarly, 7.1% of patients treated with ribociclib plus endocrine therapy and 23% of patients treated with chemotherapy discontinued at least one component of study treatment due to treatment-related adverse events.

“These findings suggest that, through the use of first-line ribociclib plus endocrine therapy, we may be able to avoid or delay chemotherapy and spare patients—even those with aggressive, life-threatening disease—the toxicities and discontinuations associated with chemotherapy,” said Professor Lu.

“To be able to extend lives, treatment compliance is key,” he added. “A treatment with improved tolerability will definitely enhance compliance and thus increase the chances of longer disease control.

“Overall, these improvements in outcomes and tolerability should translate into an evolution of our standard of care for patients with hard-to-treat breast cancer, providing clinicians with guidance for treating this patient population.”

Professor Lu said he hoped that forthcoming subgroup analyses will reveal clinical characteristics that may help physicians predict which patients will respond best to ribociclib plus endocrine therapy versus those who may respond better to chemotherapy

Funding for the study was provided by Novartis Pharma AG. Lu has received personal funding from Novartis, Roche, Merck Sharp & Dohme, Pfizer, AstraZeneca, Eisai, Eli Lilly, and Daiichi Sankyo

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