Lenvatinib Dose Escalation Is Associated With Favorable Outcomes in Patients with HCC

In a real-world analysis of patients with hepatocellular carcinoma, the median overall survival with lenvatinib was 9.7 months in the low-dose group and 7.6 months in the recommended-dose group.

Results of a real-world analysis of patients with hepatocellular carcinoma (HCC) who received single-agent lenvatinib (Lenvima) showed that dose adjustments made during treatment course were feasible and starting patients at a lower dose did not effect outcomes. A poster on the data were presented during the 2022 International Liver Cancer Association Conference.

The recommended starting dose of lenvatinib for patients with HCC is based on body weight: patients weighing 60 kg or more receive 12 mg once daily and those weighing less than 60 kg receive 8 mg once daily. The retrospective study assessed the effect of adjusting the dosage of lenvatinib using data from 6 oncology centers in Hong Kong, China.

In 174 patients, 88 (50.5%) started lenvatinib at a lower dose and 86 (49.5%) started lenvatinib at the recommended dose. The median overall survival (OS) was 9.7 months (95% CI, 9.0-10.9) in the low-dose group and 7.6 months (95% CI, 5.6-13.5) in the recommended-dose group. The difference was not significant between the group with an HR of 0.882 (95% CI, 0.60-1.30; P = .52).

“In real-world practice, it is evident that clinicians may start lower doses of lenvatinib for selected patients and/or adjust the dose during treatment according to patients’ conditions and adverse events,” the authors of the study wrote in a poser of the findings. “There are no data on the clinical impact of dose adjustment during treatment course.”

In terms of dose-adjustment data, patients were placed in group A (n = 45) defined as having had dose escalation following either a lower starting dose or previous dose reduction during treatment or group B (n = 132) defined as having had never experienced dose escalation during treatment.

The median OS was significantly better for those who had dose escalation during treatment, with a HR of 0.31 (95% CI, 0.18-0.53; P < .0001). In group A the median OS was 15.8 months (95% CI, 12.1-30.6) vs 8.0 months (95% CI, 6.4-9.5) for group B. “Patients with dose escalation during treatment remains an independent prognostic factor for OS after adjustment with other known significant prognosticators such as performance status, ALBI grading, portal vein thrombosis, and alpha fetoprotein,” the authors wrote.

In the study, 126 (71.2%) patients were Hepatitis B surface antigen–positive. Most patients had the following characteristics: Child-Pugh score A (n = 134; 75.7%), albumin-bilirubin grade 2 (n = 127, 71.8%) and BCLC stage C (n = 147; 83.0%). Over one-third of patients had advanced disease.

Investigators advised clinicians should assess patient’s conditions and determine if dose escalation of lenvatinib is a practical option, especially for those who had prior dose reduction during treatment or started with a lower dose at baseline than recommended. Introduced in 2007, sorafenib (Nexavar) was the first multikinase inhibitor approved for first line treatment of HCC. Lenvatinib was approved 2018 after showing noninferior but not statistically superior results compared with sorafenib in the REFLECT (NCT01761266) trial.2,3

A common adverse event with lenvatinib, unlike other TKIs, is associated with thyroid toxicity and monitoring for thyroid abnormalities during treatment is advised. Patients with HCC most commonly experience the adverse reactions (incidence ≥ 20%) of hypertension, fatigue, diarrhea, decreased appetite, arthralgia/myalgia, decreased weight, abdominal pain, palmar-plantar erythrodysesthesia syndrome, proteinuria, dysphonia, hemorrhagic events, hypothyroidism, and nausea.

References

  1. Chan LL, Mo FKF, Law ALY, et all. Impact of dose adjustment on clinical outcomes of Lenvatinib-treated patients with advanced hepatocellular carcinoma (HCC). Poster presented at: 16th Annual International Liver Cancer Association Conference; September 1-4, 2022; Madrid, Spain. Accessed September 7, 2022. https://bit.ly/3RrpXHf
  2. Feng MY, Chan LL, Chan SL. Drug treatment for advanced hepatocellular carcinoma: first-line and beyond. Curr Oncol.2022;29(8):5489-5507. doi:10.3390/curroncol29080434
  3. Lenvima. Prescribing information. Eisai Inc; 2021. Accessed September 7, 2022. https://bit.ly/3x0Zokc