Department of Haematology-Oncology, National University Cancer Institute Singapore (NCIS), Singapore, Singapore.
Department of Pharmacy, National University Hospital, National University Health System, Singapore, Singapore.
Int J Cancer. 2021 Jul 1;149(1):169-176. doi: 10.1002/ijc.33534. Epub 2021 Mar 6.
A dose of 200 mg 3-weekly of pembrolizumab was approved by the Food and Drug Administration (FDA) as treatment for advanced non-small cell lung cancer (NSCLC) without oncogenic drivers. This is despite evidence showing no difference in efficacy with 2 mg/kg. Our study aimed to assess the efficacy of a lower fixed dose of 100 mg, which is closer to 2 mg/kg weight-based dose in an average-sized Asian patient. All patients receiving pembrolizumab for advanced NSCLC from January 2016 to March 2020 in National University Hospital, Singapore, were included in this retrospective observational study. The effect of pembrolizumab 100 mg (Pem100) vs 200 mg (Pem200) upon survival outcomes, toxicity and cost were examined. One hundred fourteen patients received pembrolizumab. Sixty-five (57%) and 49 (43%) received Pem100 and Pem200, respectively. There was no difference in progression-free survival (PFS) and overall survival (OS) between Pem100 vs Pem200 as a single agent (PFS: 6.8 vs 4.2 months, hazard ratio [HR] 0.72, 95% confidence interval [CI] 0.36-1.46, P = .36; 9 month OS: 58% vs 63%, HR 1.08, 95% CI 0.48-2.41, P = .86) and when combined with chemotherapy (9-month PFS: 60% vs 50%, HR0.84, 95% CI 0.34-2.08, P = .71; 9-month OS: 85% vs 58%, HR 0.27, 95% CI 0.062-1.20, P = .09). No significant difference in response rate or ≥G3 immune-related toxicities between Pem100 and Pem200 was observed. A cost minimisation analysis evaluating the degree of cost savings related to drug costs estimated a within study cost saving of SGD4,290,912 and cost saving per patient of SGD39,942 in the Pem100 group. A 100 mg of pembrolizumab appears to be effective with reduction in cost. A randomised trial should be done to investigate a lower dose of pembrolizumab.
帕博利珠单抗 200mg,每 3 周一次的剂量已被美国食品和药物管理局(FDA)批准用于治疗无致癌驱动基因的晚期非小细胞肺癌(NSCLC)。尽管有证据表明,2mg/kg 与疗效无差异。我们的研究旨在评估更低固定剂量 100mg 的疗效,该剂量在平均体型的亚洲患者中更接近基于体重的 2mg/kg 剂量。所有在新加坡国立大学医院接受帕博利珠单抗治疗晚期 NSCLC 的患者均纳入本回顾性观察性研究。本研究考察了帕博利珠单抗 100mg(Pem100)与 200mg(Pem200)在生存结局、毒性和成本方面的效果。
114 名患者接受了帕博利珠单抗治疗。其中 65 名(57%)和 49 名(43%)患者分别接受了 Pem100 和 Pem200。作为单一药物,Pem100 与 Pem200 之间的无进展生存期(PFS)和总生存期(OS)无差异(PFS:6.8 与 4.2 个月,风险比[HR]0.72,95%置信区间[CI]0.36-1.46,P =.36;9 个月 OS:58%与 63%,HR 1.08,95% CI 0.48-2.41,P =.86),且联合化疗时(9 个月 PFS:60%与 50%,HR0.84,95% CI 0.34-2.08,P =.71;9 个月 OS:85%与 58%,HR 0.27,95% CI 0.062-1.20,P =.09)。
观察到 Pem100 与 Pem200 的缓解率或≥G3 免疫相关毒性无显著差异。药物成本相关成本节约程度的成本最小化分析估计 Pem100 组的研究内成本节约为 4290912 新加坡元,每位患者的成本节约为 42909.12 新加坡元。
100mg 帕博利珠单抗似乎具有疗效,且降低了成本。应该进行一项随机试验来研究较低剂量的帕博利珠单抗。