Ribociclib-Letrozole Combination as an Alternative for Neoadjuvant Chemotherapy in Selected Postmenopausal Patients with Luminal Breast Cancer (BOOG 2017-01)

PURPOSE: In hormone receptor-positive, HER2-negative, early-stage breast cancer, cyclin-dependent kinase 4 and 6 inhibition combined with endocrine therapy could represent a less toxic alternative to neoadjuvant chemotherapy (CT). The NEOLBC trial studied whether neoadjuvant ribociclib plus letrozole (RL) results in a doubling of complete cell-cycle arrest (CCCA; Ki67 <1% on IHC) compared with CT in the surgical specimen in luminal breast cancer. PATIENTS AND METHODS: This randomized phase II trial tailored neoadjuvant therapy in postmenopausal patients with early, luminal, HER2-negative, stage II/III breast cancer based on the percentage of Ki67-positive cancer cells after 2 weeks of letrozole. Patients with a Ki67 ≥1% were randomized between RL and standard CT. Secondary endpoints included pathologic response and toxicity. RESULTS: Of 161 registered patients, 70 were randomized, and 66 started the allocated treatment. The CCCA in the surgical specimen was similar for both groups: 35.3% in the RL group and 31.3% in the CT group (P = 0.73). The response according to Miller and Payne was not significantly different between the two groups, nor was the pathologic complete response rate. Overall toxicity was observed more often in the CT group. In the RL group, eight patients discontinued treatment due to toxicity, and in the CT group, 10 patients discontinued treatment. CONCLUSIONS: Although the primary endpoint was not met, the NEOLBC trial (NCT03283384) showed a similar CCCA and pathologic response for RL and CT with less toxicity. Therefore, RL as an alternative to neoadjuvant CT merits further investigation.