Safety and patient-reported outcomes in patients with hormone receptor-positive, HER2-negative advanced breast cancer treated with CDK4/6 inhibitors in China: A cross-sectional study.

person Benlong Yang Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, China info_outline Benlong Yang, Cuizhi Geng, Zhengkui Sun, Quchang Ouyang, Haibo Wang, Zhongsheng Tong, Shu Wang, Hongyuan Li, Zhaofeng Niu, Lin-Xiaoxi Ma, Jiong Wu, Yiding Chen

Authors person Benlong Yang Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, China info_outline Benlong Yang, Cuizhi Geng, Zhengkui Sun, Quchang Ouyang, Haibo Wang, Zhongsheng Tong, Shu Wang, Hongyuan Li, Zhaofeng Niu, Lin-Xiaoxi Ma, Jiong Wu, Yiding Chen Organizations Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, China, Breast Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China, Breast Surgery, Jiangxi Cancer Hospital, Nanchang, China, Hunan Cancer Hospital, Changsha, China, Breast Disease Center, The Affiliated Hospital of Qingdao University, Qingdao, China, Breast Medical Oncology, Tianjin Medical University Cancer Institute & Hospital, Tianjin, China, Department of Breast Center, Peking University People's Hospital, Beijing, China, Department of Breast and Thyroid Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China, Breast Center, Yuncheng Central Hospital, Yuncheng, China, Breast Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China Abstract Disclosures Research Funding Jiangsu Hengrui Pharmaceuticals Co., Ltd. Background: It is reported that the adverse event (AE) profile may vary with different CDK4/6 inhibitors. With the prolongation of survival, AEs occurred during the treatment period may affect quality of life (QoL) for patients with advanced disease. Currently, there has been no study focusing on the safety and patient-reported outcomes in Chinese patients treated with different CDK4/6 inhibitors. Methods: This was a large cross-sectional study conducted at 10 sites in China. Randomly selected patients with hormone receptor-positive, HER2-negative advanced breast cancer and their physicians were asked to fill the self-designed questionnaires. Disease characteristics and AEs were collected from the perspectives of both patients and physicians, while the patient questionnaire additionally included feedback on the AE management and the European Organization for Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire-breast cancer module (QLQ-BR23). Results: Between Jan 30, 2023 and Sep 15, 2023, a total of 1254 patients (median age, 55 years) were included; 212 (16.9%) patients were treated with palbociclib, 483 (38.5%) with abemaciclib, 550 (43.9%) with dalpiciclib, and 9 (0.7%) with ribociclib. Of them, 197 (15.7%) had switching history or dose adjustment of CDK4/6 inhibitor, with the main reason being AEs (51.8%). From the perspective of physicians, the most common AEs for patients were decreased white blood cell (63.3%), decreased neutrophil count (58.7%), and diarrhea (36.3%). The incidence of increased alanine aminotransaminase (ALT) and increased aspartate aminotransaminase (AST) was 9.3% (grade ≥3, 6.0%) and 8.4% (grade ≥3, 6.7%), respectively. Dalpiciclib showed the lowest incidence of increased ALT (3.5%; grade ≥3, none), increased AST (4.2%; grade ≥3, none), and diarrhea (10.5%) compared with other CDK4/6 inhibitors (P<0.001). From the perspective of patients, dalpiciclib showed the lowest incidence of fatigue, alopecia, hot flashes, insomnia, arthralgia, nausea, vomiting, diarrhea, and anorexia (P<0.05). Regarding QoL, the mean scores of upset by hair loss for different CDK4/6 inhibitors were higher than other symptom subscale scores. Dalpiciclib showed the lowest mean score of upset by hair loss compared with abemaciclib and palbociclib, whether in total (19.74 vs 27.23 vs 21.47, P=0.006) or in patients with >6 months of treatment (12.59 vs 27.78 vs 17.95, P<0.001). Conclusions: AEs are different among various CDK4/6 inhibitors. Dalpiciclib has the lowest risk of diarrhea and hepatotoxicity based on physicians' reports, and shows the best patient-perceived safety. Regarding QoL, CDK4/6 inhibitors can result in upset by hair loss, while patients have the least concern about this issue when using dalpiciclib, especially for those with long treatment duration (>6 months).