Department of Clinical Pharmacy & Toxicology, Care and Public Health Research Institute (CAPHRI), Maastricht University Medical Center+, P.O. Box 5800, 6202 AZ, Maastricht, the Netherlands.
Department of Medical Oncology, Radboud University Medical Center, Nijmegen, the Netherlands.
Target Oncol. 2018 Jun;13(3):363-370. doi: 10.1007/s11523-018-0564-3.
The impact of dose and simultaneous use of acid-reducing agents (ARAs) on the effectiveness of vemurafenib is unknown.
To determine the association between progression of metastatic BRAF V600 mutated melanoma and (1) dose reductions of vemurafenib and (2) simultaneous use of vemurafenib and ARAs.
A retrospective cohort study of 112 first-line vemurafenib users for melanoma was conducted (March 2012-March 2016), using electronic patient records and pharmacy dispensing records of a Dutch academic hospital. Cox regression analysis was used to estimate the risk of progression with full-dose (n = 64) versus reduced-dose vemurafenib (n = 48) and with simultaneous use of vemurafenib and ARAs (n = 35) versus vemurafenib alone (n = 77). Analyses were adjusted for age and sex.
In total, disease progression occurred in 55% of treated patients on vemurafenib, with a median progression-free survival of 6.0 (95% confidence interval [CI] 5.0-6.9) months. Compared to patients on vemurafenib alone, there was no increased risk of progression among patients requiring vemurafenib at a reduced dose or among patients receiving simultaneous therapy with vemurafenib and ARAs. In addition, there was no increased risk of progression among patients who used reduced-dose vemurafenib and ARAs versus those receiving full-dose vemurafenib as sole therapy. However, a tendency for progression was observed among patients who used full-dose vemurafenib and ARAs versus full-dose vemurafenib alone (adjusted hazard ratio [HRa] 2.37; 95% CI 0.97-5.76), which became statistically significant in a sensitivity analysis (HRa 4.56; 95% CI 1.51-13.75).
There was no association between the use of vemurafenib in a reduced dose or the simultaneous use of vemurafenib and ARAs and the risk of progression. In addition, there was no association between the simultaneous use of vemurafenib in a reduced dose and ARAs and the risk of progression. However, patients tolerating full-dose vemurafenib simultaneously with ARAs might have an increased risk of progression. This finding requires prospective validation.
剂量和同时使用抑酸剂（ARA）对维莫非尼疗效的影响尚不清楚。
确定转移性 BRAF V600 突变黑色素瘤的进展与（1）维莫非尼剂量减少和（2）维莫非尼与 ARA 同时使用之间的关系。
对荷兰一家学术医院的电子病历和药房配药记录进行了一项回顾性队列研究，共纳入 112 例一线维莫非尼治疗黑色素瘤患者（2012 年 3 月至 2016 年 3 月）。使用 Cox 回归分析评估全剂量（n=64）与低剂量（n=48）维莫非尼和维莫非尼与 ARA 同时使用（n=35）与维莫非尼单药治疗（n=77）相比，疾病进展的风险。分析调整了年龄和性别因素。
共有 55%的维莫非尼治疗患者发生疾病进展，中位无进展生存期为 6.0（95%置信区间[CI]：5.0-6.9）个月。与维莫非尼单药治疗组相比，需要维莫非尼低剂量治疗或同时接受维莫非尼和 ARA 治疗的患者，疾病进展风险无增加。此外，与接受维莫非尼单药治疗的患者相比，同时使用维莫非尼低剂量和 ARA 的患者，或同时使用维莫非尼高剂量和 ARA 的患者，疾病进展风险也无增加。然而，维莫非尼高剂量与 ARA 同时使用与维莫非尼高剂量单药治疗相比，进展趋势更为明显（调整后的危险比[HRa]2.37；95%CI：0.97-5.76），在敏感性分析中该差异具有统计学意义（HRa 4.56；95%CI：1.51-13.75）。
维莫非尼低剂量使用或同时使用维莫非尼和 ARA 与疾病进展风险无关。此外，维莫非尼低剂量与 ARA 同时使用与疾病进展风险无关。然而，同时耐受维莫非尼高剂量和 ARA 的患者疾病进展风险可能增加。这一发现需要前瞻性验证。
