在所有基线AFP水平上使用卡博替尼治疗HCC的改善结果

StephenW

August 18, 2020
Improved Outcomes With Cabozantinib in HCC Across All Baseline AFP Levels
Andrea S. Blevins Primeau, PhD, MBA
Cabozantinib prolonged survival of patients with previously treated advanced hepatocellular carcinoma (HCC), even among patients with high serum alpha-fetoprotein (AFP levels), according to an exploratory analysis published in Clinical Cancer Research.1

High baseline AFP has been associated with poor prognosis with HCC and systemic treatment is associated with a decrease in AFP from baseline and improved survival. AFP has not been characterized in the setting of cabozantinib treatment, which is approved by the US Food and Drug Administration for advanced HCC after progression with sorafenib. The aim of this exploratory analysis is to evaluate the role of serum AFP at baseline and changes in response to cabozantinib treatment.

The phase 3 CELESTIAL trial randomly assigned 707 patients with previously treated advanced HCC to receive cabozantinib or placebo. Cabozantinib was demonstrated to prolong overall survival (OS) and progression-free survival (PFS) compared with placebo.

This analysis stratified patients from the CELESTIAL trial according to baseline AFP levels, using 400 ng/mL as a cutoff. Changes in serum AFP were assessed at 8 weeks, which coincided with the first tumor assessment in the trial. AFP response was defined as a ≥20% decrease from baseline.

Baseline AFP levels were similar between the cabozantinib and placebo arms, with medians of 154.7 ng/mL (interquartile range [IQR], 14.0-2998.9) and 202.5 ng/mL (IQR, 10.2-5174.9), respectively.

Cabozantinib treatment resulted in prolonged OS compared with placebo in both baseline AFP groups, but was significant only among patients with a higher baseline AFP level. Among patients with lower baseline AFP levels, the median OS was 13.9 months with cabozantinib compared with 10.3 months with placebo (hazard ratio [HR], 0.81; 95% CI, 0.62-1.04). In the group with higher AFP levels, cabozantinib resulted in a median OS of 8.5 months compared with 5.2 months with placebo (HR, 0.71; 95% CI, 0.54-0.94).

PFS was also longer with cabozantinib in both baseline AFP groups. In the group with low baseline AFP levels, the median PFS with cabozantinib was 5.5 months compared with 1.9 months with placebo (HR, 0.47; 95% CI, 0.37-0.60). Among patients with higher baseline AFP levels, the median PFS was 3.9 and 1.9 months with cabozantinib or placebo, respectively (HR, 0.42; 95% CI, 0.32-0.55).

AFP response occurred more frequently with cabozantinib, with a rate of 50% compared with 13% in the placebo group. AFP response was associated with longer OS and PFS, regardless of treatment. Among the cabozantinib-treated patients, the median OS with an AFP response was 16.1 months compared with 9.1 months for patients who did not experience an AFP response (HR, 0.61; 95% CI, 0.41-0.74). Among patients who received placebo, the median OS with an AFP response was 11.3 months compared with 7.2 months with no response (HR, 0.79; 95% CI, 0.41-1.55).

In the cabozantinib arm, the median PFS was 7.3 months with an AFP response compared with 4.0 months with no AFP response (HR, 0.55; 95% CI, 0.41-0.74). In the placebo arm, the median PFS was 3.8 or 1.9 months with or without an AFP response, respectively (HR, 0.51; 95% CI, 0.27-0.96).

“Our analysis shows improved outcomes with cabozantinib relative to placebo in patients with previously treated HCC across a range of baseline AFP levels,” the authors wrote. They noted that given the number of emerging therapies for HCC, “further investigation of AFP kinetics in patients treated with newly available therapies is warranted.”

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Reference

Kelley RK, Meyer T, Rimassa L, et al. Serum alpha-fetoprotein levels and clinical outcomes in the phase III CELESTIAL study of cabozantinib versus placebo in patients with advanced hepatocellular carcinoma. Clin Cancer Res. Published July 29, 2020. doi: 10.1158/1078-0432.CCR-19-3884

StephenW

2020年8月18日
在所有基线AFP水平上使用卡博替尼治疗HCC的改善结果
Andrea S.Blevins Primeau，博士，工商管理硕士
根据《临床癌症研究》上发表的一项探索性分析，卡博替尼可延长先前接受过治疗的晚期肝细胞癌（HCC）患者的生存，甚至在血清甲胎蛋白（AFP水平）高的患者中也是如此。

基线AFP高与HCC预后差有关，而全身治疗与基线AFP降低及生存期延长有关。 AFP尚未以卡博替尼治疗为特征，该药已获美国食品和药物管理局批准在索拉非尼治疗后用于晚期HCC。这项探索性分析的目的是评估血清AFP在基线时的作用以及对卡博替尼治疗的反应变化。

CELESTIAL的3期试验随机分配了707例先前接受过治疗的晚期HCC患者接受卡博替尼或安慰剂。与安慰剂相比，卡波替尼可延长总体生存期（OS）和无进展生存期（PFS）。

该分析根据基线AFP水平将CELESTIAL试验中的患者分层，以400 ng / mL作为临界值。在第8周评估血清AFP的变化，这与该试验中首次肿瘤评估相吻合。 AFP反应定义为与基线相比下降≥20％。

卡博替尼和安慰剂组的基线AFP水平相似，分别为154.7 ng / mL（四分位间距[IQR]，14.0-2998.9）和202.5 ng / mL（IQR，1.2-5174.9）。

在两个基线AFP组中，卡博替尼治疗均导致与安慰剂相比OS延长，但仅在基线AFP水平较高的患者中显着。在基线AFP水平较低的患者中，卡博替尼的中位OS为13.9个月，而安慰剂为10.3个月（危险比[HR]，0.81； 95％CI，0.62-1.04）。在AFP水平较高的组中，卡博替尼的OS中位数为8.5个月，而安慰剂为5.2个月（HR，0.71； 95％CI，0.54-0.94）。

在两个基线AFP组中，卡博替尼的PFS也更长。在基线AFP水平较低的组中，卡博替尼的中位PFS为5.5个月，而安慰剂为1.9个月（HR，0.47； 95％CI，0.37-0.60）。在基线AFP水平较高的患者中，卡博替尼或安慰剂的中位PFS分别为3.9和1.9个月（HR，0.42； 95％CI，0.32-0.55）。

卡博替尼对AFP的反应更为频繁，发生率为50％，而安慰剂组为13％。无论治疗如何，AFP反应均与更长的OS和PFS相关。在接受卡博替尼治疗的患者中，具有AFP反应的中位OS为16.1个月，而未经历AFP反应的患者的中位OS为9.1个月（HR，0.61； 95％CI，0.41-0.74）。在接受安慰剂的患者中，有AFP反应的中位OS为11.3个月，而无反应的为7.2个月（HR，0.79； 95％CI，0.41-1.55）。

在卡博替尼组中，AFP应答的中位PFS为7.3个月，而无AFP应答的中位PFS为4.0个月（HR，0.55； 95％CI，0.41-0.74）。在安慰剂组中，有或无AFP反应的中位PFS分别为3.8个月或1.9个月（HR，0.51； 95％CI，0.27-0.96）。

作者写道：“我们的分析显示，在一系列基线AFP水平下，卡博替尼相对于先前接受过治疗的HCC患者的安慰剂疗效有所改善。”他们指出，鉴于HCC新兴疗法的数量众多，“有必要进一步研究接受新疗法治疗的患者的AFP动力学。”

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参考

Kelley RK，Meyer T，Rimassa L等。晚期肝细胞癌患者卡博替尼与安慰剂的III期临床研究的血清甲胎蛋白水平和临床结果。临床癌症研究。 2020年7月29日发布。doi：10.1158 / 1078-0432.CCR-19-3884