Three-Drug Combo Proves Efficacious, Safe in Unresectable Liver Cancer

Combining PD-1 immune checkpoint inhibition with transarterial chemotherapy and Lenvima (lenvatinib) was shown to improve outcomes for patients with unresectable hepatocellular carcinoma (HCC), the most common type of primary liver cancer, according to findings from a recent study.

The researchers decided to combine these agents because of the promise they have previously shown in this patient population. Additionally, transarterial chemoembolization (TACE) – which is when chemotherapy is delivered to the arteries during a non-invasive procedure – and hepatic arterial infusion chemotherapy (HAIC) is recommended for patients with intermediate or advanced HCC.

“Because HCC is a tumor with rich blood supply, TACE or HAIC can improve the concentration of chemotherapy drugs to the tumor, which can improve the curative effect on the one hand, and reduce the systemic (side effects) on the other hand,” study authors Wei Lu, Tianqiang Song and Mengran Lan, said in an interview with CURE®.

Researchers analyzed 35 patients being treated at Tianjin Cancer Hospital in China, with intermediate/advanced HCC who underwent therapy with Lenvima, PD-1 inhibition and transarterial therapy (LEN-PD1-TH) and compared outcomes for patients who only received Lenvima and PD-1 inhibition therapy (LEN-PD1).

The main goal of the study was progression-free survival, which is how long a patient lives without their disease progressing. Secondary endpoints included analyzing overall survival and overall response rate, which is the percentage of patients on the study whose disease shrunk as a result from the treatment.

At an average follow-up of 14 months, the LEN-PD1-TH groups had a longer median progression-free survival of 15 months, compared to 9 months in the LEN-PD1 group. The three-drug group also had better overall survival, as an average length of survival could not be established because so many people were still alive. In the LEN-PD1 group, average survival was about 14 months.

The LEN-PD1-TH cohort had more than twice the response rate than the LEN-PD1 group, at 42.9% and 20.1%, respectively.

“This study is the first to report that the efficacy of (Lenvima) combined with PD-1 inhibitors and interventional therapy is better than that of (Lenvima) combined with PD-1 inhibitors when the baseline level is balanced and the number of people in the two groups is the same,” the researchers said. “Based on this, we hope our results can provide a theoretical basis or enlightenment for future related research.”

The researchers also conducted subgroup analyses on the study population and found that certain patients were more likely to benefit from the three-drug combination. They were patients who were: younger than the age of 65; had liver cirrhosis; Child-Pugh class A (which predicts prognosis and liver function); metastasis outside of the liver; no vascular invasion; tumors smaller than 10 cm and more than 3 tumors; Barcelona Clinic liver cancer stage C, which indicates varied liver functioning; and AFP (a protein in blood that may indicate liver cancer) at or under 400 ng/ml.

Seventy patients enrolled in the study were also involved in the safety analysis. Among them, the most common severe (grade 3 or higher) side effect was hypertension (high blood pressure) in both the LEN-PD1-TH group and LEN-PD1 group, at 20% and 17.1%, respectively.

There were also two grade 3 hand-foot-skin reactions and one grade 3 bleeding event in the group of patients who received Lenvima and PD-1 therapy. In the Lenvima, PD-1 therapy and transarterial therapy group, there was one case pf grade 3 decreased blood platelet count, and one grade 3 muscle pain event. Based on these data, the researchers determined that there was not a significant difference in side effects between the two groups.

After discovering that Lenvima, PD-1 inhibition and transarterial therapy is safe and effective, the researchers are hoping to conduct further studies with the combination.

“The next step is to continue to collect patients, expand cases, and continue follow-up. If possible, we intend to conduct prospective research to further verify our conclusions,” they said.

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