Abstract P3-07-07: The use of ribociclib/letrozole combination as an alternative for neoadjuvant chemotherapy in selected patients with early luminal breast cancer
Authors: de Groot Anne Florine , Cohen Danielle , Heijns Joan B. , Mandigers Caroline , Keizer Diederick M. , Putter Hein , Kranenbarg Elma Meershoek-Klein , Carpentier Marjolijn Duijm-de , Dijkstra Kyra , van Leeuwen-Stok Elise , Liefers Gerrit-Jan , Linn Sabine , Kroep Judith 
Published: March 2023

Abstract
Introduction In hormone receptor-positive, HER2-negative early-stage breast cancer (BC), cyclin-dependent kinases 4 and 6 inhibition (CDK4/6i) in combination with endocrine therapy (ET) could represent an alternative to neoadjuvant chemotherapy (NAC). Methods NEOLBC is a randomized phase II trial that tailored neoadjuvant therapy in postmenopausal patients with early, luminal (ER &gt;50%, PR any), HER2-negative, stage II/III BC based on the percentage of Ki67 positive cancer cells after a window of opportunity of two weeks letrozole. Patients with a Ki67 &gt;= 1% after 2 weeks were randomized between ribociclib plus letrozole (RL) and chemotherapy (CT; AC-T regimen). The primary objective was to determine if RL gives a doubling in complete cell cycle arrest (CCCA; Ki67 &lt; 1% on IHC) as compared to CT in the surgical specimen (70% vs. 35% of patients, respectively). Secondary endpoints included pathological response, toxicity and ER pathway activity (measured by the OncoSIGNal qPCR test). Results Out of 161 registered patients, 70 patients were randomized and 66 patients started treatment; 34 RL and 32 CT. Patient characteristics were equally distributed between the two groups, except for the PR status (RL 23.5% negative vs. 50.0% negative in the CT group). In the intention to treat analysis, 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 pathological complete response (pCR) in the breast was not significantly different between the two groups (11.8% vs. 3.1%, p = 0.36) nor was the pCR rate in breast plus lymph nodes (8.8% vs. 3.1%, p = 0.61) for the RL vs. CT group, respectively. An explorative analysis on the difference in Ki67% (decline, no change, increase) from baseline to surgery showed a decline in 73.5% vs. 50.0%, no change in 17.6% vs. 31.3% and an increase in 8.8% vs. 18.8% of patients (p = 0.06) for the RL vs. CT group, respectively. In the RL group eight patients (23.5%) discontinued ribociclib early due to toxicity (two SAE’s were observed) vs. 10 patients (31.3%) discontinuing treatment in the CT group (one SAE was observed). Secondary endpoints, including the ER pathway activity analysis, will be presented in-depth during the meeting. Conclusion Although the primary endpoint was not met, the NEOLBC trial showed a similar CCCA and pathological response at surgery for RL vs. CT. Therefore, RL as an alternative for NAC merits further investigation in follow-up studies. ClinicalTrials.gov: NCT03283384
Citation Format: Anne Florine de Groot, Danielle Cohen, Joan B. Heijns, Caroline Mandigers, Diederick M. Keizer, Hein Putter, Elma Meershoek-Klein Kranenbarg, Marjolijn Duijm-de Carpentier, Kyra Dijkstra, Elise van Leeuwen-Stok, Gerrit-Jan Liefers, Sabine Linn, Judith Kroep. The use of ribociclib/letrozole combination as an alternative for neoadjuvant chemotherapy in selected patients with early luminal breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-07-07.