卡博替尼与瑞戈非尼治疗晚期肝细胞癌的疗效比较。
Comparative Efficacy of Cabozantinib and Regorafenib for Advanced Hepatocellular Carcinoma.
机构信息
UCSF, Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA.
Ipsen Pharma, Boulogne-Billancourt, France.
出版信息
Adv Ther. 2020 Jun;37(6):2678-2695. doi: 10.1007/s12325-020-01378-y. Epub 2020 May 18.
BACKGROUND
No trials have compared cabozantinib and regorafenib for the second-line treatment of advanced hepatocellular carcinoma (HCC).
OBJECTIVES
Conduct a matching-adjusted indirect comparison (MAIC) of the efficacy and safety of second-line cabozantinib and regorafenib in patients with advanced HCC and disease progression after prior sorafenib.
METHODS
The CELESTIAL and RESORCE trials were used for indirect comparison of second-line cabozantinib and regorafenib in advanced HCC. Population-level data were available for RESORCE, individual patient data (IPD) for CELESTIAL. To align with RESORCE, the CELESTIAL population was limited to patients who received first-line sorafenib only. To minimize potential effect-modifying population differences, the CELESTIAL IPD were weighted to balance the distribution of clinically relevant baseline characteristics with those of RESORCE. Overall survival (OS) and progression-free survival (PFS) were evaluated for the matching-adjusted second-line CELESTIAL population and compared with those for RESORCE using weighted Kaplan-Meier curves and parametric modeling. Rates of grade 3/4 treatment-emergent adverse events (TEAEs) affecting > 5% of patients in any study arm were compared.
RESULTS
In the matching-adjusted second-line populations (CELESTIAL, effective sample size = 266; RESORCE, n = 573), median (95% confidence interval) OS was similar for cabozantinib and regorafenib (11.4 [8.9-17.0] versus 10.6 [9.1-12.1] months; p = 0.3474, log-rank test). Median PFS was longer for cabozantinib than regorafenib (5.6 [4.9-7.3] versus 3.1 [2.8-4.2] months; p = 0.0005, log-rank test). There was a trend for lower rates of some grade 3/4 TEAEs with regorafenib than with cabozantinib, which may reflect the exclusion of sorafenib-intolerant patients from RESORCE but not from CELESTIAL, a difference that the MAIC methods could not remove. Only diarrhea rates were statistically significantly lower for regorafenib (p ≤ 0.001).
CONCLUSIONS
Cabozantinib may achieve similar OS and prolonged PFS compared with regorafenib in patients with progressive advanced HCC after prior sorafenib.
背景
尚无试验比较卡博替尼和瑞戈非尼作为索拉非尼治疗后进展的晚期肝细胞癌（HCC）二线治疗药物的疗效。
目的
采用匹配调整间接比较（MAIC），比较二线卡博替尼和瑞戈非尼在先前接受索拉非尼治疗后疾病进展的晚期 HCC 患者中的疗效和安全性。
方法
CELESTIAL 和 RESORCE 试验用于二线卡博替尼和瑞戈非尼治疗晚期 HCC 的间接比较。RESORCE 提供了人群水平的数据，CELESTIAL 提供了个体患者数据（IPD）。为了与 RESORCE 保持一致，将 CELESTIAL 人群限制为仅接受一线索拉非尼治疗的患者。为了最小化潜在的影响修正人群差异，对 CELESTIAL IPD 进行加权，以平衡具有临床意义的基线特征分布与 RESORCE 的分布。使用加权 Kaplan-Meier 曲线和参数建模评估匹配调整后的二线 CELESTIAL 人群的总生存期（OS）和无进展生存期（PFS），并与 RESORCE 进行比较。比较任何研究组中发生率超过 5%的治疗相关不良事件（TEAEs）的等级 3/4。
结果
在匹配调整后的二线人群中（CELESTIAL，有效样本量=266；RESORCE，n=573），卡博替尼和瑞戈非尼的中位（95%置信区间）OS 相似（11.4[8.9-17.0]与 10.6[9.1-12.1]个月；p=0.3474，对数秩检验）。卡博替尼的中位 PFS 长于瑞戈非尼（5.6[4.9-7.3]与 3.1[2.8-4.2]个月；p=0.0005，对数秩检验）。与卡博替尼相比，瑞戈非尼的某些 3/4 级 TEAEs 发生率呈下降趋势，这可能反映了 RESORCE 排除了不耐受索拉非尼的患者，但 CELESTIAL 并未排除，MAIC 方法无法消除这种差异。只有瑞戈非尼的腹泻发生率有统计学意义上的降低（p≤0.001）。
结论
与瑞戈非尼相比，卡博替尼可能在先前接受索拉非尼治疗后进展的晚期 HCC 患者中实现相似的 OS 和延长的 PFS。
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