Randomized phase II clinical trial and biomarker analysis of paclitaxel plus epirubicin versus vinorelbine plus epirubic
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CLINICAL TRIAL
Randomized phase II clinical trial and biomarker analysis of paclitaxel plus epirubicin versus vinorelbine plus epirubicin as neoadjuvant chemotherapy in locally advanced HER2‑negative breast cancer with TEKT4 variations Yi‑Zhou Jiang1,2,3,4,5 · Li‑Ping Ge1,2,3,4 · Xi Jin1,2,3,4 · Lei Fan1,2,3,4 · Min He1,2,3,4 · Yin Liu1,2,3,4 · Li Chen1,2,3,4 · Wen‑Jia Zuo1,2,3,4 · Jiong Wu1,2,3,4,5 · Guang‑Yu Liu1,2,3,4,5 · Gen‑Hong Di1,2,3,4,5 · Zhong‑Hua Wang1,2,3,4,5 · Ke‑Da Yu1,2,3,4,5 · Zhi‑Ming Shao1,2,3,4,5 Received: 8 July 2020 / Accepted: 12 September 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Purpose Resistance to paclitaxel remains a major challenge in treating breast cancer. Our preclinical study suggested that TEKT4 germline variations in breast cancer are associated with paclitaxel resistance and increase vinorelbine sensitivity. This clinical trial compared the efficacy of paclitaxel and vinorelbine in breast cancer neoadjuvant chemotherapy. Methods In this open-label, single-center, phase II trial, female patients with human epidermal growth factor receptor 2 (HER2)-negative, stage IIB–IIIC breast cancer harboring TEKT4 germline variations were randomly assigned to the paclitaxel plus epirubicin (PE) or vinorelbine plus epirubicin (NE). The primary endpoint was the pathologic complete response (pCR) rate, and the secondary endpoints were the objective response rate (ORR) and safety. Targeted sequencing of a panel comprising 484 breast-related genes was performed to identify pCR-associated somatic mutations in each group. Results 91 Patients were assigned to PE (46 patients) or NE (45 patients). NE numerically increased the pCR rate (22.2% versus 8.7%, P = 0.074). The ORRs for NE and PE were 82.2% and 76.1%, respectively. Interestingly, NE (15.4%) showed a significantly higher pCR rate than PE (0%) in the hormone receptor (HR)-positive subgroup (P = 0.044). Both regimens were well tolerated, with grade 3 and 4 toxicities reported at the expected levels. The biomarker analysis showed that UNC13D mutation predicted the pCR rate in NE (P = 0.011). Conclusions Although the primary endpoint was not met, NE might bring clinical benefit to HR-positive patients or patients simultaneously carrying UNC13D mutations. Keywords Breast cancer · Clinical trial · Neoadjuvant chemotherapy · Germline variation · Paclitaxel resistance · Pathologic complete response
Yi-Zhou Jiang, Li-Ping Ge, and Xi Jin have contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10549-020-05940-8) contains supplementary material, which is available to authorized users. * Zhong‑Hua Wang [email protected] * Ke‑Da Yu [email protected] * Zhi‑Ming Shao [email protected] Extended author information available on the last page of the article
Abbreviations CI Confidence interval CR Complete response ER Estrogen receptor HER2 Human epidermal growth factor receptor 2 HR Hormone receptor ITT Intent-to-trea
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