Phase II study of neoadjuvant weekly paclitaxel and carboplatin with lapatinib in HER2+ breast cancer.

• DOI: 10.1200/jco.2014.32.15_suppl.619
• Publication Date: 2019-01-03T22:24:40Z
• Authors: Andrea Li Ann Wong; Sing Huang Tan; I Peng Thomas Soh; Chee Seng Tan; Yi Wan Lim; Angela Pang; Jingshan Ho; Samuel Guan Wei Ow; Raghav Sundar; Mei-Yan Pang; Ching-Wan Chan; Shaik Ahmad Buhari; Mikael Hartman; Philip Iau; Anthony Tang; Nan-Soon Wong; Yoon Sim Yap; Bee-Luan Khoo; Jean Paul Thiery; Soo-Chin Lee
• Keywords: Lapatinib; Carboplatin; Tolerability; Regimen

619^ Background: The optimal neoadjuvant regimen in HER2+ breast cancer is undefined. We evaluated the efficacy and tolerability of weekly paclitaxel/carboplatin with lapatinib. Methods: stage I-III patients received 4 cycles 3 PCL [IV paclitaxel (P) 80mg/m2 (days 1, 8, 15), carboplatin (C) AUC 2 8), oral lapatinib (L) (750mg daily)] followed by surgery. Lapatinib dose reductions were not allowed. Patients pCR (ypT0N0) adjuvant PCL; those without doxorubicin/cyclophosphamide. All 1 year trastuzumab at investigators’ discretion, concurrent 1000mg/day for 52 weeks (neoadjuvant + adjuvant). Primary endpoint was pCR; secondary endpoints clinical CR/PR, toxicities DFS. Results: 36 recruited (Chinese/Malay/Others: 52.8/36.1/11.1%). Median age diagnosis 51 (29-78) years. 69.4%, 63.9%, 80.6% 61.1% had cT3/4, cN+, grade hormone receptor positive tumors. 63.9% achieved CR/PR after cycles. At surgery, 33.3% ypN0, 11.1% pCR, which limited to cN0 tumors (n=8; 50% pCR). 21 month median follow-up, DFS 83.3%. G3/4 non-hematologic occurred 19.4%, mainly from non-neutropenic infections (11.1%) gastrointestinal (8.3%). None developed cardiac dysfunction. lower mean relative intensity all drugs (P: 0.61 0.33 vs 0.91 0.16, p=0.002; C: 0.65 0.30 0.95 0.14, p=0.001; L: 0.62 0.34 0.97 0.10, p<0.01) rates (40% 90.3%, p=0.024) than without. Dose interruptions 37.1%, 34.4%, 11.4%) 16.7%. 19.5%) common. Serial samples 5 showed general progressive decline circulating tumor cells treatment but remained measurable before Conclusions: While low rate contributed advanced tumors, difficult maintain its efficacy/toxicity ratio favorable unselected patients. Tumor immunohistochemistry pharmacogenetic studies are ongoing select most likely benefit. Clinical trial information: NCT01309607.