肾功能受损在癌症患者中很常见，可以改变药物的药代动力学，从而影响药物的安全性和有效性。我们评估了在治疗采用环松赛因为基因依赖性蛋白激酶4/6抑制剂期间肾功能受损的影响，并确定了肾功能受损的晚期乳腺癌患者的剂量推荐。我们综合评估了在无癌症受试者的I期专门的肾功能受损研究和六项I-III期的癌症患者试验中的药代动力学、安全性和有效性数据。在专门的肾功能受损研究中，与正常肾功能的受试者相比，在单个400毫克剂量下，环松赛因的药代动力学曝光在肾功能受损的受试者中更高。然而，在患者试验中，正常肾功能、轻度/中度肾功能受损患者在推荐的起始剂量600毫克下，单个剂量和稳态下的环松赛因曝光量是相近的。对于肾功能受损的晚期乳腺癌患者，模型预测的稳态曝光量也在肾功能组之间相似。在晚期乳腺癌患者中，无论是在正常、轻度/中度肾功能受损的肾功能群体中，无进展生存期相似，安全概况也一般保持一致，仅出现低等级和可控的不良事件，展现了积极的收益风险比。从综合证据和考虑实际临床情况的角度看，对于轻度/中度肾功能受损的患者不建议进行剂量调整，而对于重度肾功能受损的患者，则建议减少剂量。本报告提出了一种全面的创新策略，以确定肾功能受损患者的剂量，并证明了整合临床药理学研究和患者试验数据来证明肾功能受损患者的剂量的有效性。Clinicaltrials.gov识别号：NCT02431481，NCT01958021，NCT02422615，NCT02278120，NCT01237236，NCT01898845，NCT01872260.©2023.作者。

Renal impairment is common in patients with cancer and can alter the PK and thus the safety and efficacy of drugs. We assessed the impact of renal impairment during treatment with ribociclib, a cyclin-dependent kinase 4/6 inhibitor, and determined dose recommendations for patients with advanced breast cancer with renal impairment.A comprehensive assessment integrating pharmacokinetic, safety, and efficacy data from a phase I dedicated renal impairment study in non-cancer subjects and six phase I-III trials in patients with cancer was performed.Ribociclib showed higher pharmacokinetic exposure in subjects with renal impairment than those with normal renal function following a single 400-mg dose in the dedicated renal impairment study. However, in patient trials, both single-dose and steady‑state ribociclib exposure was comparable between patients with cancer with mild/moderate renal impairment and those with normal renal function following the recommended starting dose of 600 mg. Model-predicted steady‑state exposure in patients with advanced breast cancer was also similar across the renal function groups. Progression-free survival was similar and safety profiles were generally consistent across the renal cohorts (normal/mild/moderate) in patients with advanced breast cancer, with low-grade and manageable adverse events, demonstrating a positive benefit-risk profile.From the collective evidence and considering a real-world clinical setting, no dose adjustment is recommended for patients with mild/moderate renal impairment, whereas a reduced dose is recommended for patients with severe renal impairment. This report presented a holistic and innovative strategy to determine dose in patients with renal impairment and demonstrated the effectiveness of integrating the data of both a clinical pharmacology study and patient trials to justify doses in patients with renal impairment.Clinicaltrials.gov identifiers: NCT02431481, NCT01958021, NCT02422615, NCT02278120, NCT01237236, NCT01898845, NCT01872260.© 2023. The Author(s).