The Real-World Data in Japanese Patients with Unresectable Hepatocellular Carcinoma Treated with Lenvatinib from a Nationwide Multicenter Study

Abstract

Background: Lenvatinib (LEN) has been approved for patients with unresectable hepatocellular carcinoma (u-HCC) since March 2018 in Japan. We performed a retrospective nationwide multicenter study to clarify the clinical characteristics of LEN in real-world practice. Methods: A total of 343 u-HCC patients who received LEN from March 2018 to May 2020 at 23 sites in Japan were registered. Results: During the median observation period of 10.5 months, 143 patients died. In Child-Pugh A (n = 276) and Child-Pugh B (n = 67) patients, the median overall survival (OS) was 21.0 and 9.0 months. The median progression-free survival (PFS) was 8.8 months in Child-Pugh A patients. The objective response rate (ORR) and disease control rate (DCR) according to modified response evaluation criteria in solid tumors (RECIST criteria) were 42.1% and 82.1%. The independent pretreatment factors associated with mortality in all patients were AFP ≥ 400 ng/mL (hazard ratio (HR) 2.00, 95% confidential interval (95% CI) 1.08–2.09, p < 0.0001), modified albumin-bilirubin (ALBI) grade 2b or 3 (HR 1.56, 95% CI 1.09–2.17, p = 0.012), major vascular invasion (HR 1.91, 95% CI 1.26–2.89, p = 0.0022), PS > 0 (HR 1.50, 95% CI 1.09–2.08, p = 0.014), and MTT (molecular targeted therapy) experience (HR 2.22, 95% CI 1.56–3.13, p = 0.00038). In the MTT naïve patients with ALBI grade 1 or modified ALBI 2a and BCLC stage B (n = 68), median OS and PFS were 25.3 and 12.3 months. Liver-related adverse events during LEN were the only significant adverse event associated with OS (HR 2.74, 95% CI 1.93–3.88, p < 0.0001). Among the Child-Pugh A patients with extrahepatic metastasis and no major vascular invasion, median PFS in the patients with bone metastasis was significantly shorter than those with lung or adrenal grand metastasis (6.3 vs. 12.5 months, p = 0.0025). Conclusion: LEN showed a high response rate in real-world practice. Pretreatment factors, including ALBI score, AFP, and major vascular invasion are important in making a treatment strategy for patients with u-HCC. The patients with bone metastasis would be candidates for new therapeutic approaches.

Conventional Therapies Do Not Prolong the Prognosis of Hepatocellular Carcinoma Patients with Extrahepatic Metastases under Receiving of Tyrosine Kinase Inhibitors

“…This could have been partly attributed to the characteristics of our hospital, in which, patients with bone metastases are referred for radiation therapy. Although some reports demonstrated that bone metastases had a better prognosis compared to other metastatic sites, [23,24] mixed data have been reported regarding the prognosis among metastatic sites [25]. Notably, our data showed no significant difference between bone and lung metastases.…”

Incidence and risk of hypertension with lenvatinib in treatment of solid tumors: An updated systematic review and meta‐analysis

“…Lenvatinib is well known for improving the PFS and OS of cancer patients, and the efficacy of Lenvatinib in the treatment of solid tumors has been well‐demonstrated in exciting literature. 16 , 17 , 18 However, these studies did not mention the incidence of Lenvatinib‐related adverse events in relation to TD, PFS, and OS. Therefore, we also performed a subgroup analysis to explore the relationship between duration, PFS, and OS HTN incidence.…”

Impact of modified albumin–bilirubin grade on survival in patients with HCC who received lenvatinib

“…In addition, overall survival was significantly better in patients with ALBI grade 1 than in those with ALBI grade 2 (HR, 0.12; 95%CI, 0.02–0.97); p < 0.01) 22 . Very recently, Tsuchiya et al 23 investigated the factors associated with overall survival in 343 patients with unresectable HCC who were treated with lenvatinib. They found that ECOG-PS ≥ 1 (HR, 1.50; 95%CI, 1.09–2.08; p = 0.014), mALBI grade 2b/3 (HR, 1.56; 95%CI, 1.09–2.17; p = 0.012), α-fetoprotein ≥ 400 (HR, 2.00; 95%CI, 1.42–2.80; p < 0.001), major vascular invasion (HR, 1.91; 95%CI, 1.26–2.89; p = 0.002), and molecular targeted therapy experience (HR, 2.22; 95%CI, 1.56–3.13; p < 0.001) were independently associated with overall survival in the multivariate analysis.…”