School of Medicine, Vita-Salute San Raffaele University, Milan, Italy.
Unit of Oncology, Università Vita-Salute, IRCCS-San Raffaele Scientific Institute, via Olgettina 70, 20132, Milan, Milano, Italy.
J Cancer Res Clin Oncol. 2021 Dec;147(12):3665-3671. doi: 10.1007/s00432-021-03602-w. Epub 2021 Mar 20.
Recently, three published phase III trials highlighted the superiority of investigational drugs compared to placebo, thus leading to their approval in the second-line setting. We report here a MAIC of second-line MKI options for patients with HCC previously treated with sorafenib using individual real-world data of regorafenib and aggregate data of second-line cabozantinib from the CELESTIAL trial.
Data from 278 patients who received regorafenib as second-line therapy after sorafenib failure for unresectable HCC were used as IPD. Data inclusion were adapted to those reported in the CELESTIAL trial in the subset of patients who received sorafenib as the only prior therapy. Survival medians and rates were obtained from Kaplan-Meier curves, and differences between regorafenib and cabozantinib groups were explored through Cox regression adjusted for weights originating from MAIC.
The median OS of the weighted regorafenib group was 11.1 months (IQR: 5.6-16.4) and 11.3 (IQR: 6.7-22.4) for cabozantinib; HR 0.83 (95%CI 0.62-1.09). The median PFS of the weighted regorafenib group was 3.0 months (IQR: 1.9-4.8) and 5.5 (IQR: 2.3-9.3) for cabozantinib; HR 0.50 (95%CI 0.41-0.62). In the subgroup who received prior sorafenib for < 3 months, the median OS of the regorafenib group was 6.5 months (IQR: 4.7-10.9) and 9.5 months (IQR: 5.9-18.2) for cabozantinib; HR 0.68 (95%CI 0.39-1.16). In the subgroup receiving prior sorafenib for 3 to < 6 months, the median OS of the regorafenib group was 8.0 months (IQR: 4.2-15.2) and 11.5 (IQR: 6.5-23.9) for cabozantinib; HR 0.66 (95%CI 0.42-1.02). In the subgroup receiving prior sorafenib for ≥ 6 months, the median OS of the regorafenib group was 13.4 (IQR: 8.1-46.5) and 12.3 (IQR: 6.6-22.9) for cabozantinib; HR 0.89 (95%CI 0.52-1.51).
Our results confirmed no differences between regorafenib and cabozantinib in terms of OS. However, in earlier progressors on prior sorafenib a larger benefit might be expected from cabozantinib treatment.
最近，三项已发表的 III 期试验强调了研究药物与安慰剂相比的优越性，从而导致它们在二线治疗中获得批准。我们在此报告了使用regorafenib 的个体真实世界数据和 CELESTIAL 试验二线卡博替尼的汇总数据，对先前接受索拉非尼治疗的 HCC 患者的二线 MKI 选择进行 MAIC。
使用 278 名患者的数据，这些患者在不可切除 HCC 中接受索拉非尼失败后接受regorafenib 作为二线治疗，作为 IPD。数据纳入适应于那些在仅接受索拉非尼作为唯一先前治疗的患者亚组中报告的 CELESTIAL 试验。通过 Kaplan-Meier 曲线获得生存中位数和生存率，通过 Cox 回归调整来自 MAIC 的权重来探索 regorafenib 组和卡博替尼组之间的差异。
加权 regorafenib 组的中位 OS 为 11.1 个月（IQR：5.6-16.4），卡博替尼组为 11.3 个月（IQR：6.7-22.4）；HR 0.83（95%CI 0.62-1.09）。加权 regorafenib 组的中位 PFS 为 3.0 个月（IQR：1.9-4.8），卡博替尼组为 5.5 个月（IQR：2.3-9.3）；HR 0.50（95%CI 0.41-0.62）。在先前接受索拉非尼治疗<3 个月的亚组中，regorafenib 组的中位 OS 为 6.5 个月（IQR：4.7-10.9），卡博替尼组为 9.5 个月（IQR：5.9-18.2）；HR 0.68（95%CI 0.39-1.16）。在先前接受索拉非尼治疗 3-<6 个月的亚组中，regorafenib 组的中位 OS 为 8.0 个月（IQR：4.2-15.2），卡博替尼组为 11.5 个月（IQR：6.5-23.9）；HR 0.66（95%CI 0.42-1.02）。在先前接受索拉非尼治疗≥6 个月的亚组中，regorafenib 组的中位 OS 为 13.4 个月（IQR：8.1-46.5），卡博替尼组为 12.3 个月（IQR：6.6-22.9）；HR 0.89（95%CI 0.52-1.51）。
我们的结果证实，在 OS 方面，regorafenib 和卡博替尼之间没有差异。然而，在先前进展较快的患者中，卡博替尼治疗可能会带来更大的获益。
