Zhaolun Cai1, Chunyu Liu2, Chen Chang3, Chaoyong Shen4, Yuan Yin5, Xiaonan Yin6, Zhiyuan Jiang7, Zhou Zhao8, Mingchun Mu9, Dan Cao10, Lingli Zhang11, Bo Zhang12. 1. Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China. Electronic address: caizhaolun@foxmail.com. 2. Department of Pharmacy, West China Second University Hospital, Sichuan University, Chengdu 610041, Sichuan, China; Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu 610041, Sichuan, China; Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu 610041, Sichuan, China; West China School of Pharmacy, Sichuan University, Chengdu 610041, Sichuan, China. Electronic address: chunyu_liu@foxmail.com. 3. Department of Abdominal Oncology, Cancer Center of West China Hospital, Sichuan University, Chengdu 610041, China. Electronic address: changch1008@163.com. 4. Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China. Electronic address: scyshenchaoyong@163.com. 5. Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China. Electronic address: yinyuan10@hotmail.com. 6. Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China. Electronic address: yxnyinxiaonan@163.com. 7. Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China. Electronic address: dr.jiangzhiyuan@foxmail.com. 8. Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China. Electronic address: zhaozhou_med@163.com. 9. Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China. Electronic address: 609485922@qq.com. 10. Department of Abdominal Oncology, Cancer Center of West China Hospital, Sichuan University, Chengdu 610041, China. Electronic address: caodan316@163.com. 11. Department of Pharmacy, West China Second University Hospital, Sichuan University, Chengdu 610041, Sichuan, China; Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu 610041, Sichuan, China; Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu 610041, Sichuan, China; West China School of Pharmacy, Sichuan University, Chengdu 610041, Sichuan, China. Electronic address: zhanglingli@scu.edu.cn. 12. Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China; Research Laboratory of Tumor Epigenetics and Genomics for General Surgery, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, China. Electronic address: hxwcwk@126.com.
Abstract
BACKGROUND: We aimed to evaluate comparative safety and tolerability of the approved PARP inhibitors in people with cancer. METHODS: Eligible studies included randomized controlled trials comparing an approved PARP inhibitor (fluzoparib, olaparib, rucaparib, niraparib, or talazoparib) with placebo or chemotherapy in cancer patients. Outcomes of interest included: serious adverse event (SAE), discontinuation due to adverse event (AE), interruption of treatment due to AE, dose reduction due to AE, and specific grade 1-5 AEs. RESULTS: Ten trials including 3763 participants and six treatments (olaparib, rucaparib, niraparib, talazoparib, placebo, and protocol-specified single agent chemotherapy) were identified. SAE and discontinuation of treatment did not differ significantly among the four approved PARP inhibitors. Regarding interruption of treatment and dose reduction due to AE, statistically significant differences and statistically non-significant trend were observed. Talazoparib is associated with a higher risk of interruption of treatment and dose reduction (excluding rucaparib) due to AE as compared with the other drugs. Niraparib showed a trend of lower risk of AE related dose reduction as compared with the other drugs. Furthermore, there were significant differences in specific grade 1-5 AE among the four drugs. CONCLUSION: The safety profile of the four approved PARP inhibitors is comparable in terms of SAE and AE-related discontinuation of treatment. Statistically significant differences in the AEs spectrum and AEs related dose interruption and dose reduction demonstrated the prompt identification of AE and dose personalization seem mandatory to obtain maximal benefit from PARP inhibitors.
BACKGROUND: We aimed to evaluate comparative safety and tolerability of the approved PARP inhibitors in people with cancer. METHODS: Eligible studies included randomized controlled trials comparing an approved PARP inhibitor (fluzoparib, olaparib, rucaparib, niraparib, or talazoparib) with placebo or chemotherapy in cancer patients. Outcomes of interest included: serious adverse event (SAE), discontinuation due to adverse event (AE), interruption of treatment due to AE, dose reduction due to AE, and specific grade 1-5 AEs. RESULTS: Ten trials including 3763 participants and six treatments (olaparib, rucaparib, niraparib, talazoparib, placebo, and protocol-specified single agent chemotherapy) were identified. SAE and discontinuation of treatment did not differ significantly among the four approved PARP inhibitors. Regarding interruption of treatment and dose reduction due to AE, statistically significant differences and statistically non-significant trend were observed. Talazoparib is associated with a higher risk of interruption of treatment and dose reduction (excluding rucaparib) due to AE as compared with the other drugs. Niraparib showed a trend of lower risk of AE related dose reduction as compared with the other drugs. Furthermore, there were significant differences in specific grade 1-5 AE among the four drugs. CONCLUSION: The safety profile of the four approved PARP inhibitors is comparable in terms of SAE and AE-related discontinuation of treatment. Statistically significant differences in the AEs spectrum and AEs related dose interruption and dose reduction demonstrated the prompt identification of AE and dose personalization seem mandatory to obtain maximal benefit from PARP inhibitors.