Abstract GS2-06: Primary results of SOLTI-1402/CORALLEEN phase 2 trial of neoadjuvant ribociclib plus letrozole versus chemotherapy in PAM50 Luminal B early breast cancer: An open-label, multicenter, two-arm, randomized study
Authors: Gavilá Joaquín , Saura Cristina , Pascual Tomás , Hernando Cristina , Muñoz Montserrat , Paré Laia , Farré Blanca González , Fernandez Pedro , Galván Patricia , Farré Xavier González , Oliveira Mafalda , Gil Miguel Gil , Arumi Miriam , Tur Neus Ferrer , Montaño Alvaro , Izarzugaza Yan , Cussac Antonio Llombart , Bratos Raquel , González Santiago , Martínez Eduardo , Hoyos Sergio , Rojas Beatriz , Virizuela Juan Antonio , Ortega Vanesa , López Rafael , Céliz Pamela , Ciruelos Eva , Villagrasa Patricia , Prat Aleix 
Published: March 2020

Background: Different approaches for treatment de-escalation are being investigated; however, the current ongoing phase III adjuvant trials with CDK4/6 inhibitors are not addressing the question if these drugs can replace multi-agent chemotherapy in high-risk early breast cancer. Here, we present the primary results of the CORALLEEN phase 2 trial, which evaluates the efficacy of ribociclib plus endocrine therapy (ET) as neoadjuvant treatment in patients with high-risk Luminal B disease. Methods: CORALLEEN is a parallel, multicenter, two-arm, randomized exploratory study in postmenopausal women with primary operable hormone receptor-positive (HR+)/HER2-negative breast cancer, Luminal B by Prosigna®. Other eligibility criteria include stage I-III operable breast cancer and ECOG 0-1. Patients were randomized 1:1 to receive either six 28-days cycles of ribociclib (600mg; 3-weeks-on/1-week-off) plus daily letrozole (2.5mg) or chemotherapy (CT): 4 cycles of AC (doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 every 21 days) followed by weekly paclitaxel (80 mg/m2) during 12 weeks. Baseline, Day 15 on-treatment, and surgical specimens were collected for molecular characterization and evaluation of response. The primary endpoint is the rate of PAM50 Risk of Relapse (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 (i.e. &gt;90% distant relapse-free survival at 10 years). ROR-low was defined using the standard cutpoints as &lt;40 points if pathologically node-negative (at surgery) and &lt;15 points if 1-3 positive nodes (at surgery). The trial was designed to estimate the rate of ROR-low disease at surgery in each arm without a formal comparison. A total of 47 evaluable patients per arm and an expected ROR-low rate of 25%, would allow a precision of the estimate between 11.5% and 12.4%. Secondary endpoints included safety, intrinsic subtype at surgery, residual cancer burden (RCB), and Preoperative Endocrine Prognostic Index (PEPI). Results: From July 2017 to November 2018, 198 patients were screened with Prosigna® across 21 sites in Spain. From these, 106 (54%) patients with Luminal B disease were recruited, and 96 (90.6%) completed treatment as planned. Main baseline patient characteristics were similar between both treatment arms: mean age 64, mean tumor size 3.8 cm, N+ 39%, mean Ki67 33.2%, and mean ROR score 72.9 (86.8% were ROR-high). A total of 101 (95.3%) surgical samples were analyzed. ROR-low rates at surgery in the ribociclib+ET and CT arms were 48% (95%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 patients in the ribociclib+ET arm and in 84.3% in the CT arm. The rates of RCB0/1 and PEPI 0 in the ribociclib+ET 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 CT arm were 11.8% (95%CI 4.4-23.9) and 17.6% (95%CI 8.4-30.9). Grade 3-4 toxicities were observed in 54.9% of the patients in the ribociclib+ET arm and 69.2% in the CT arm. Additional correlative molecular analyses will be presented. Conclusions: Neoadjuvant ribociclib and letrozole in high-risk Luminal B breast cancer achieves similar rates of ROR-low disease at surgery as multi-agent 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.

Citation Format: Joaquín Gavilá, Cristina Saura, Tomás Pascual, Cristina Hernando, Montserrat Muñoz, Laia Paré, Blanca González Farré, Pedro Fernandez, Patricia Galván, Xavier González Farré, Mafalda Oliveira, Miguel Gil Gil, Miriam Arumi, Neus Ferrer Tur, Alvaro Montaño, Yan Izarzugaza, Antonio Llombart Cussac, Raquel Bratos, Santiago González, Eduardo Martínez, Sergio Hoyos, Beatriz Rojas, Juan Antonio Virizuela, Vanesa Ortega, Rafael López, Pamela Céliz, Eva Ciruelos, Patricia Villagrasa, Aleix Prat. Primary results of SOLTI-1402/CORALLEEN phase 2 trial of neoadjuvant ribociclib plus letrozole versus chemotherapy in PAM50 Luminal B early breast cancer: An open-label, multicenter, two-arm, randomized study [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr GS2-06.