Lenvima May Prolong Survival in Advanced Liver Cancer That Progressed on Immunotherapy

Patients with advanced hepatocellular carcinoma (HCC) whose disease progressed on immunotherapy may derive a survival benefit when treated with second-line Lenvima (lenvatinib), findings from a recent analysis demonstrated.

In particular, from the time that Lenvima was given to patients, the median progression-free survival (the time when a patient lives with cancer without worsening) was 3.7 months and median overall survival (the time when a patient with cancer is still alive) was 12.8 months. These results, which were presented at the 2023 Gastrointestinal Cancers Symposium, are comparable with survival findings from other studies using Lenvima as first-line therapy (initial treatment).

However, investigators, including Dr. Jennifer Gile, a hematology/oncology fellow at the Mayo Clinic in Rochester, Minnesota, looked to determine the optimal sequencing therapy for patients following progression on immunotherapy. As a result, an analysis was created to evaluate this in patients with advanced HCC who were diagnosed between 2010 and 2021.

The primary goals that were assessed in this trial were overall survival and progression-free survival.

Progression After Immunotherapy

Investigators identified 53 patients (median age, 67 years; 83% men) with advanced HCC who were treated with Lenvima following immunotherapy. Lenvima was given to 85% of patients in the second-line setting (treatment given when the initial treatment did not work or stopped working) and to 15% of patients in the third-line setting (when the initial treatment and subsequent treatment doesn’t work or stops working) or later. Of note, 72% of patients had died when researchers extracted these data.

Regarding safety, the most common side effects of any grade were fatigue (53%), high blood pressure (37%), aspartate aminotransferase (AST) elevation (a sign of liver or heart damage, cancer or other diseases; 30%), anorexia (28%), bilirubin elevation (the substance that forms when red blood cells break down that may result in jaundice; 25%) and diarrhea (25%).

Forty percent of patients reported severe or worse side effects. These included high blood pressure (25%), confusion (6%), acute kidney injury (2%), high levels of potassium in the blood (2%), alanine aminotransferase elevation (potentially indicating liver damage; 2%), proteinuria (high levels of protein in urine; 2%), joint pain (2%), heart failure (2%), AST elevation (2%), bilirubin elevation (2%), pain and swelling of the hands or feet (2%), sores in the mouth (2%), weight loss (2%), underactive thyroid (2%), anorexia (2%), fatigue (2%) and diarrhea (2%).

Additionally, treatment was stopped due to side effects in seven patients, including fatigue in two patients, confusion in two patients and heart failure, high blood pressure and elevated bilirubin in one patient each.

First-Line Therapy for HCC

Lenvima is a multikinase inhibitor that gained approval by the Food and Drug Administration in the first-line setting for patients with advanced HCC. However, Tecentriq (atezolizumab) and Avastin (bevacizumab) are considered new standards of care as first-line therapy based on findings from the IMBrave150 trial.

In the IMBrave150 trial, the combination of Tecentriq and Avastin led to statistically significant and clinically meaningful improvements in overall survival and progression-free survival compared with Nexavar (sorafenib).

A total of 501 patients were followed for a median of 15.6 months. The median overall survival seen was 19.2 months with the combination versus 13.4 months with Nexavar, and the median progression-free survival was 6.8 months versus 4.3 months, respectively. Treatment with Tecentriq plus Avastin also led to an improved confirmed objective response rate versus Nexavar at 27.3% versus 11.9 % with Nexavar. In the combination arm, ongoing responses were seen in 86.5% compared with 68.4% of the Nexavar arm.

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