A prospective, phase II, neoadjuvant clinical study based on chemotherapy sensitivity in hormone receptor–positive, HER2-negative breast cancer: FINEST study.
Authors: Chen Li , Li Junjie , Wang Zhonghua , Wu Wenya , Li Huajun 
Published: June 2023

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Background: Neoadjuvant therapy for hormone receptor positive/HER2-negative breast cancer presents challenges in patient selection and treatment modalities. Chemotherapy and endocrine therapy are neoadjuvant options for this type of breast cancer. Neoadjuvant endocrine therapy (NET) has a similar response rate to chemotherapy. However, patient selection is a key factor. We designed this study to further optimize the selection of target population and treatment strategy. Methods: For breast cancer patients eligible for inclusion, patients were allocated to 2 cycles of chemotherapy using nab-paclitaxel with carboplatin. For patients with better efficacy (≥40% regression after 2 cycles), the original regimen was continued to complete 6 cycles (group A). For patients who had poor efficacy ( <40% regression after 2 cycles), patients were randomly assigned (1:3:1) to group B, C, D. Group B continued to use the same chemotherapy. Group C were received dalpiciclib, letrozole and adebrelimab plus goserrelin if patient was premenopausal. Group D were directly received surgery. Primary endpoints were pathologic complete response (pCR) rate and objective response rate (ORR). As the trial progresses, according to Bayesian model, the posterior distribution of pCR rates of group C would be updated. To explore the genomic feature, a genetic panel which includes 484 genes that are targets of approved and experimental therapies and frequently mutated genes in breast cancer was used. Results: From Nov 16, 2020 to Jun 10, 2022, 121 patients were enrolled. 76 patients with better efficacy were continued to complete 6 cycles (group A). And 45 patients were randomly assigned to groups C (27 patients), B (9 patients) and D (9 patients). The primary objective was not met. The total pCR rate was 4.1% (5/121) with all pCR patients are in group A. No significant differences were observed in pCR between group B, C and D. ORR was 81.8% in total cohort with 100% in group A, 20% in group B, 81.5% in group C and 0% in group D, respectively. Decreases in Ki-67 were similar across arms. According to the Bayesian model, there is no probability of success of phase 3 study. Therefore, the study was closed. Our analysis illustrated the most prevalent mutations were PIK3CA (41%), followed by TP53 (28%) and GATA3 (17%). We found that AKAP3, ASXL1, INSR, RET or TBX3 mutations were related to the limited treatment benefit of chemotherapy. Mutations in MAP3K1 were likely to be associated with the worse outcome in Group C. Conclusions: Neoadjuvant chemotherapy and neoadjuvant endocrine therapy are not mutually exclusive. The overall treatment strategy did not improve the efficacy, but there is still a possibility that some people can get an improvement from the strategy adjustment. Precision analysis may yield the characteristics of patients who would benefit from this shift in treatment strategy. Clinical trial information: NCT04215003 .