Author(s): Li Chen, MD1,2; Hui Li, MD3; Hao Zhang, MD4; Huawei Yang, MD5; Jun Qian, MD6; Zhihua Li, MD7; Yu Ren, MD8; Shu Wang, MD9; Peifen Fu, MD10; Hongjian Yang, MD11; Yunjiang Liu, MD12; Jing Sun, MD13; Jianyun Nie, MD14; Ruiwen Lei, MD15; Yongzhong Yao, MD16; Anqin Zhang, MD17; Shouman Wang, MD18; Xiaopeng Ma, MD19; Zhong Ouyang, MD20; Hongwei Yang, MD21; Song-Yang Wu, MD1,2; Shuo-Wen Cao, MD1,2; Kun Wang, MD22; Aimei Jiang, MD23; Quchang Ouyang, MD24; Da Pang, MD25; Limin Wei, MD26; Xiaoming Zha, MD27; Yu Shen, PhD28; Xiangwen Qu, MD28; Fei Wu, MD28; Xiaoyu Zhu, PhD28; Zhonghua Wang, MD1,2; Lei Fan, MD1,2; Zhi-Ming Shao, MD1,2;
The CamRelief Randomized Clinical Trial
IMPORTANCE
Preferred neoadjuvant strategies for early or locally advanced triple-negative breast cancer include a 4-drug chemotherapy regimen containing anthracyclines, cyclophosphamide, taxanes, and platinum. Blockade of the programmed death receptor 1/ligand-1 (PD-1/PD-L1) pathway may improve efficacy of classic neoadjuvant chemotherapy. Camrelizumab, an anti–PD-1 antibody, has showed antitumor activity in advanced triple-negative breast cancer.
OBJECTIVE
To evaluate the efficacy and adverse events of camrelizumab plus chemotherapy vs placebo plus chemotherapy as neoadjuvant therapy for patients with early or locally advanced triple-negative breast cancer.
DESIGN, SETTING, AND PARTICIPANTS
This randomized, double-blind, phase 3 trial enrolled patients from 40 hospitals in China between November 25, 2020, and May 12, 2023 (data cutoff: September 30, 2023). A total of 441 eligible patients were enrolled.
INTERVENTIONS
Patients were randomized in a 1:1 ratio to receive either camrelizumab 200 mg (n = 222) or placebo (n = 219) combined with chemotherapy every 2 weeks. The chemotherapy included nab-paclitaxel (100 mg/m2) and carboplatin (area under the curve, 1.5) on days 1, 8, and 15 in 28-day cycles for the first 16 weeks followed by epirubicin (90 mg/m2) and cyclophosphamide (500 mg/m2) every 2 weeks for 8 weeks.
MAIN OUTCOMES AND MEASURES
The primary end point was pathological complete response (defined as no invasive tumor in breast and lymph nodes [ypT0/Tis ypN0]).
RESULTS
Among 441 females randomized (median age, 48 years), the median (range) follow-up duration from randomization was 14.4 (0.0-31.8) months. Pathological complete response was achieved in 126 patients (56.8% [95% CI, 50.0%-63.4%]) in the camrelizumab-chemotherapy group and 98 patients (44.7% [95% CI, 38.0%-51.6%]) in the placebo-chemotherapy group (rate difference, 12.2% [95% CI, 3.3%-21.2%]; 1-sided P = .004). In the neoadjuvant phase, adverse events of grade 3 or higher occurred in 198 patients (89.2%) in the camrelizumab-chemotherapy group and 182 (83.1%) in the placebo-chemotherapy group; serious adverse events occurred in 77 patients (34.7%) in the camrelizumab-chemotherapy group and 50 (22.8%) in the placebo-chemotherapy group, with fatal adverse events occurring in 2 patients (0.9%) in the camrelizumab-chemotherapy group.
CONCLUSIONS AND RELEVANCE
Among patients with early or locally advanced triple-negative breast cancer, the addition of camrelizumab to neoadjuvant chemotherapy significantly improved pathological complete response.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT04613674
Author Affiliations
1Department of Breast Surgery, Fudan University Shanghai Cancer Center and Key Laboratory of Breast Cancer in Shanghai; 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; 3Department of Breast Surgery, Sichuan Provincial Cancer Hospital, Chengdu, China; 4Department of Breast Surgery, Nanyang City Center Hospital, Nanyang, China; 5Department of Breast Surgery, Guangxi Medical University Affiliated Cancer Hospital, Nanning, China; 6Department of Surgical Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China; 7Breast Center Second Section, The Third Hospital of Nanchang, Nanchang, China; 8Department of Breast Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China; 9Department of Breast Surgery, Peking University People’s Hospital, Beijing, China; 10Department of Breast Surgery, The First Affiliated Hospital of Zhejiang University, Hangzhou, China; 11Department of Breast Surgery, Zhejiang Cancer Hospital, Hangzhou, China; 12Department of Breast Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China; 13The Fifth Ward of Medical Oncology, Anyang Tumour Hospital, Anyang, China; 14Department of Breast Surgery, Yunnan Cancer Hospital, Kunming, China; 15Department of Breast Surgery, Yuebei People’s Hospital, Shaoguan, China; 16Department of Breast Surgery, Nanjing Drum Tower Hospital, Nanjing, China; 17Department of Breast Surgery, Guangdong Women’s and Children’s Hospital, Guangzhou, China; 18Department of Medical Oncology, Xiangya Hospital of Central South University, Changsha; 19Department of Breast Surgery, Anhui Provincial Hospital, Hefei, China; 20Department of Breast Surgery, The First Affiliated Hospital of Xiamen University, Xiamen, China; 21Breast and Thyroid Surgery, Suining Central Hospital, Suining, China; 22Breast Center Second Section, Guangdong General Hospital, Guangzhou, China; 23Department of Breast Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, China; 24Department of Breast Medicine, Hunan Cancer Hospital, Changsha, China; 25Department of Breast Surgery, Affiliated Cancer Hospital of Harbin Medical University, Harbin, China; 26Department of Breast Surgery, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China; 27Department of Breast Surgery, Jiangsu Provincial Hospital, Nanjing, China; 28Jiangsu Hengrui Pharmaceuticals Co., Ltd, Shanghai, China;