Purpose: In hormone receptor-positive, HER2-negative, early-stage breast cancer (BC), cyclin-dependent kinases 4 and 6 inhibition (CDK4/6i) combined with endocrine therapy could represent a less toxic alternative to neoadjuvant chemotherapy (NAC). The NEOLBC trial studied whether neoadjuvant ribociclib plus letrozole (RL) gives a doubling in complete cell cycle arrest (CCCA; Ki67 <1% on immunohistochemistry) as compared to chemotherapy (CT) in the surgical specimen in luminal BC.
Patients and methods: This randomized phase II trial tailored neoadjuvant therapy in postmenopausal patients with early, luminal, HER2-negative, stage II/III BC based on the percentage of Ki67 positive cancer cells after two weeks letrozole. Patients with a Ki67 ≥1% were randomized between RL and standard CT. Secondary endpoints included pathological response and toxicity.
Results: Of 161 registered patients, 70 patients were randomized and 66 patients started allocated treatment. The CCCA in the surgical specimen was similar for both groups: 35.3% in the RL vs. 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 pathological complete response (pCR) rate. Overall toxicity was observed more often in the CT group. In the RL group eight patients discontinued treatment due to toxicity vs. 10 patients in the CT group.
Conclusion: Although the primary endpoint was not met, the NEOLBC trial (NCT03283384) showed a similar CCCA and pathological response for RL vs. CT with less toxicity. Therefore, RL as an alternative for NAC merits further investigation.