Gemcitabine with Cisplatin or Paclitaxel in Metastatic Triple-negative Breast Cancer Xi-Chun Hu*, Binghe Xu, Li Cai, Zhong Hua Wang, Biyun Wang, Jian Zhang, Yuee Teng, Zhongsheng Tong, Yueyin PAN, Yongmei Yin, Changping Wu, Zefei Jiang, Xiaojia Wang, Guyin Lou, Donggeng Liu, Ji Feng Feng, Jianfeng Luo, Jiong Wu, Zhimin Shao *Department of Medical Oncology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China Background: There is still no standard chemotherapy for patients with metastatic triple-negative breast cancer (mTNBC). The doublet of gemcitabine and carboplatin (GC) is recommended in NCCN guidelines based on two phase II/III trials, however, it has never been compared with standard chemotherapy for metastatic breast cancer. Our previous phase II trial in patients with mTNBC (clinicaltrials.gov Identifier: NCT ) suggested a median progression- free survival (PFS) of 6.2 months with first-line use of gemcitabine and cisplatin (GP), an already fully assessed regimen in human cancer. Methods: A hybrid trial design incorporating a formal test of superiority as well as noninferiority was applied to compare the GP and GT (gemcitabine/ paclitaxel) regimens as first- line treatment on PFS of mTNBC in the Chinese Breast Cancer Study Group (CBCSG) 006 trial (clinicaltrials.gov Identifier: NCT ). We randomly assigned 240 mTNBC patients with no previous exposure to palliative chemotherapy to receive GP regimen (1250 mg/m 2 d1,8/ 75 mg/m 2 d1) or GT regimen (1250 mg/m 2 d1,8 /175 mg/m 2 d1) with expected median PFS improvement of 1.2 months. Conclusions: GP regimen is better than GT regimen in terms of objective response and PFS, which met our primary endpoint. The toxicity profile of the two regimens was different without any unexpected findings. A total number of 236 subjects received either GP regimen or GT regimen, 118 subjects in each arm. The enrollment was from January 2011 through November As of ， the number of PFS events was 201 while the number of OS events was 97. The objective response rate of GP regimen, in comparison with GT regimen, was （ 67.9 ％ vs ％， P = ）， PFS was （ median 232 days vs.194 days ， P = ） and the overall survival was （ median 672 days vs. 556 days ， P = ）。 The relative dose intensity of the three drugs was 90% and above ， the total administration period for GP and GT arm was 654 and 648 days, respectively. Adverse events GT(n=118) Any Grade Grade 3-4 No. (%) GP(n=118) Any Grade Grade 3-4 No. (%) Leukocytopenia108 (91.5)55 (46.6)107 (90.7)57 (48.3) Neutropenia103 (87.3)69 (58.5)107 (90.7)67 (56.8) Febrile Neutropenia 3 (2.5) Anemia78 (66.1)#6 (5.1)#104 (88.1)39 (33.1) Thrombocytopenia39 (33.1)#3 (2.5)#74 (62.7)38 (32.2) Hematological AE #Statistically Difference Adverse events GT(n=118) Grade 1-4 Grade 3- 4 No. (%) GP(n=118) Grade 1-4 Grade 3-4 No. (%) Alopecia42(35.6)#NA12 (10.2)NA Nausea57 (48.3)#1(0.8)*92 (78.0)8 (6.8) Vomiting40 (33.9)#1(0.8)#86 (72.9)13(11.0) Anorexia10 (8.5)#1 (0. 8) 33 (28.0)2 (1.7) Stomatitis7 (5.9)1 (0.8)4 (3.4)0 Constipation10 (8.5)#026 (22.0)0 Diarrhea10 (8.5)05 (4.2)0 Fatigue23 (19.5)2 (1.7)33 (28.0)1 (0.8) Dyspnea4 (3.4)2 (1.7)1(0.8)0 Fever15 (12.7)013 (11.0)1 (0.8) Peripheral Neural Toxicity 59 (50.0)#2 (1.7)26 (22.0)0 Rash21 (17.8)012 (10.2)0 Nephrotoxicity0000 Hematuria0000 Vertigo2 (1.7)04 (3.4)0 Ototoxicity2 (1.7)05 (4.2)1 (0.8) Ache9 (7.6)012 (10.2)1 (0.8) Pneumonia1 (0.8)02 (1.7)1 (0.8) Hemorrhage1 (0.8)000 Allergic Reaction 3 (2.5) 00 Infection3 (2.5)1 (0.8)00 Limb Edema7 (5.9)15 (4.2)0 Non-Hematological AE