Author: By Lynda Williams, Senior medwireNews Reporter
medwireNews: CORALLEEN trial findings suggest neoadjuvant ribociclib and letrozole might allow some postmenopausal women with stage I–IIIA breast cancer deemed at high risk according to their PAM50 risk of relapse (ROR) to avoid chemotherapy before surgery.
“The results of this study suggest that specific patients with high-risk, early stage, hormone receptor-positive, HER2-negative breast cancer could achieve molecular downstaging of their disease with CDK4/6 inhibitor and endocrine therapy”, say Aleix Prat, from Hospital Clínic of Barcelona in Spain, and co-authors in The Lancet Oncology.
The open-label phase II trial enrolled 106 patients classified by PAM50 as intrinsic subtype luminal B, 87% of whom had a high PAM50 ROR at baseline based on gene expression, tumour size and nodal status, while 13% had an intermediate ROR.
The patients were randomly assigned to receive six 28-day cycles of ribociclib 600 mg/day on a 3 weeks on, 1 week off schedule, plus letrozole 25 mg/day or to receive four 21-day cycles of doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 plus 12 weekly doses of paclitaxel 80 mg/m2.
At time of surgery, 46.9% of the 52 patients assigned to receive ribociclib plus letrozole were reclassified as low ROR, as were 46.1% of the 49 participants given chemotherapy. A conversion to intrinsic subtype luminal A occurred in 87.8% and 92.7% of the groups, respectively, and both arms achieved a reduction in Ki67 score.
A pathological complete response in breast and axillary lymph nodes was achieved by none of the patients given ribociclib plus letrozole and 6.1% had a residual cancer burden of 0–1 versus 5.8% and 11.8% of those given chemotherapy. The corresponding rates for objective response were 57.1% and 78.8%, with breast-conserving surgery achieved for 85.7% and 72.2%, respectively.
Ribociclib plus letrozole was associated with grade 1–2 neutropenia (57%), elevated alanine aminotransferase (26%) and asthenia, while alopecia (100%), neutropenia (69%) and asthenia (54%) were the most common grade 1–2 adverse events (AEs) with chemotherapy. Grade 3–4 AEs occurred in 57% and 69% of the treatment arms, respectively, and ribociclib plus letrozole was associated with grade 1–3 QTc prolongation in two patients.
Noting that the NeoPAL study of pablociclib plus letrozole in a similar patient population indicated that “less than 20% of patients might not need chemotherapy”, the investigators comment: “Overall, the results of the NeoPAL and CORALLEEN trials suggest that a treatment strategy free from chemotherapy is an alternative worth exploring in future neoadjuvant or adjuvant trials in patients with high-risk luminal B disease.
“However, whether preoperative endocrine prognostic index, ROR, or both, is the best biomarker to identify this patient population is unknown,” they remark.
The research was simultaneously presented at the San Antonio Breast Cancer Symposium in Texas, USA, and published in The Lancet Oncology.
Prat A, Saura C, Pascual T, et al. Ribociclib plus letrozole versus chemotherapy for postmenopausal women with hormone receptor-positive, HER2-negative, luminal B breast cancer (CORALLEEN): an open-label, multi-centre, randomised, phase 2 trial. Lancet Oncol; Advance online publication 11 December 2019. https://doi.org/10.1016/S1470-2045(19)30786-7
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