A phase II study by Gavilá et al evaluating the efficacy of the combination of the CDK4/6 inhibitor ribociclib and the aromatase inhibitor letrozole in combination as a neoadjuvant treatment in patients with high-risk luminal B breast cancer has found that the therapy produced response rates similar to multiagent chemotherapy—with less toxicity. The study was presented at the 2019 San Antonio Breast Cancer Symposium (Abstract GS2-06) and was simultaneously published in The Lancet Oncology.

Between 10% and 20% of all breast cancers are classified as luminal B disease. This cancer is often diagnosed in younger women and tends to carry a poorer prognosis than luminal A tumors.

Study Methodology

From July 2017 to November 2018, the researchers enrolled 106 patients with high-risk luminal B stage I–III breast cancer into the randomized CORALLEEN phase II trial. CORALLEEN investigated the efficacy ribociclib/letrozole vs multiagent chemotherapy as neoadjuvant therapy. A total of 101 surgical samples were analyzed.

The primary endpoint of the study was the rate of PAM50-based Prosigna risk of recurrence (ROR)-low disease at surgery in each arm. PAM50 ROR score integrates gene-expression data, tumor size, and nodal status to define a low-risk group in the adjuvant setting.

Study Results

The researchers found ROR-low rates at surgery in the ribociclib/letrozole and chemotherapy arms were 48% (95% confidence interval [CI] = 33.7–62.6) and 47.1% (95% CI = 32.9–61.5), respectively. Intrinsic subtype conversion to luminal A at surgery occurred in 88% of the patients in the ribociclib/letrozole arm and in 84.3% in the chemotherapy arm. The rates of low residual cancer burden (RCB0/1) and Preoperative Endocrine Prognostic Index (PEPI 0) in the ribociclib/letrozole arm were 8% (95% CI = 2.2–19.2) and 24% (95% CI = 13.1–38.2), respectively. The rates of RCB0/1 and PEPI 0 in the chemotherapy arm were 11.8% (95% CI = 4.4–23.9) and 17.6% (95% CI = 8.4–30.9).

Grade 3 or 4 toxicities were observed in 54.9% of the patients in the ribociclib/letrozole arm and 69.2% in the chemotherapy arm. Additional correlative molecular analyses will be presented during the San Antonio Breast Cancer Symposium.

“Neoadjuvant ribociclib and letrozole in high-risk luminal B breast cancer achieves similar rates of ROR-low disease at surgery as multiagent chemotherapy. Future studies in high-risk early breast cancer evaluating the survival outcomes and quality of life of this combination in the absence of cytotoxic therapy are justified,” concluded the study authors.

Clinical Significance

“Our results indicate that neoadjuvant treatment with a combination of ribociclib and letrozole has similar clinical benefits as standard multiagent chemotherapy, and with less toxicity,” said lead study author Joaquin Gavilá, MD, a medical oncologist at the Instituto Valenciano de Oncologia in Valencia, Spain, in a statement. “We believe that this combination is worth exploring as an alternative to chemotherapy for patients with high-risk luminal B breast cancer.” Dr. Gavilá also cautioned that the results from this study are preliminary and need to be confirmed in future clinical trials.

Disclosure: The SOLTI-1402/CORALLEEN study was sponsored by Novartis, the Breast Cancer Research Foundation, the American Association for Cancer Research, and Breast Cancer Now Career Catalyst. For full disclosures of the study authors, visit abstractsonline.com or thelancet.com.