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For patients with unresectable, non-metastatic hepatocellular carcinoma, Lenvima plus Keytruda in combination with TACE improved outcomes.
Lenvima plus Keytruda in combination with TACE improved outcomes for patients with unresectable non-metastatic hepatocellular carcinoma.
Among patients with unresectable, non-metastatic hepatocellular carcinoma, treatment with Lenvima (Lenvatinib) plus Keytruda (pembrolizumab) in combination with transarterial chemoembolization (TACE) was found to improve outcomes when compared with treatment with TACE plus placebo, researchers have stated.
Findings from the phase 3 LEAP-012 study were published in The Lancet.
“In summary, [Lenvima] plus [Keytruda] in combination with TACE showed significant and clinically meaningful improvement in progression-free survival and a numerical improvement in overall survival compared with placebo combined with TACE in this global randomized study,” concluded Dr. Masatoshi Kudo and colleagues in the study. “Based on these data, [Lenvima] plus [Keytruda] combined with TACE could be a new treatment option for patients with unresectable, non-metastatic hepatocellular carcinoma.”
Kudo is a professor and Chairman at the Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine in Osaka, Japan.
Unresectable: a tumor that cannot be removed by surgery.
Non-metastatic: when cancer has not spread beyond where it started.
Progression-free survival: the time a patient lives without their disease spreading or worsening.
Overall survival: the time that a patient lives, regardless of disease status.
Objective response rate: the percentage of patients who responded partially or completely to treatment.
Hepatic failure: liver failure.
Myositis: inflammation of the muscles
TACE, according to the Cleveland Clinic, is a procedure that involves injecting a combination of cancer-fighting drugs and an embolic agent, which blocks blood flow, into a tumor. The treatment is intended to cut off the blood supply to the tumor with little to no effect on liver functioning.
Researchers noted in the study that in hepatocellular carcinoma managed with TACE, median progression-free survival remains poor at approximately seven to eight months, “and so improved outcomes for patients with unresectable, non-metastatic hepatocellular carcinoma are urgently needed.”
Lenvima, as explained by the National Cancer Institute, blocks proteins in order to prevent cancer cells from growing and kill them, and may also prevent the growth of new blood vessels needed by tumors to grow. Keytruda binds to the protein PD-1 on the surface of immune cells, which prevents cancer from suppressing the immune system, the National Cancer Institute explained.
“Combining [Keytruda] with a multikinase inhibitor such as [Lenvima] could increase anti-tumor activity by suppressing the pro-tumor immune microenvironment and preventing neovascularization, which could augment the effect of TACE,” Kudo and colleagues wrote in the study.
In the study, 480 patients were enrolled and assigned between May 22, 202 and Jan. 11, 2023 to receive TACE plus Lenvima plus Keytruda (237 patients) or TACE plus placebo (243 patients). Patients had a median age of 66 years old, 398 (83%) were male and 347 (72%) were Asian.
With a median follow-up of 25.6 months as of a data cutoff of Jan. 30, 2024, the median progression-free survival was 14.6 months in the Lenvima plus Keytruda arm, with 132 progression-free survival events: There were 20 deaths and 112 progressions, researchers reported. Median progression-free survival in the placebo arm was 10 months with 154 events: There were eight deaths and 146 progressions.
The objective response rate was 47% in the Lenvima plus Keytruda arm and 33% in the placebo arm, with the median duration of response being 12.6 months in the Lenvima plus Keytruda arm 10.7 months in the placebo arm and the median time to progression being 16.6 months in the Lenvima plus Keytruda arm and 10.3 months in the placebo arm.
Researchers reported that 69 patients, or 29%, in the Lenvima plus Keytruda arm died, as did 82, or 34%, of the placebo group, and 24-month overall survival rates were 75% and 69%.
Grade 3 (severe) or worse treatment-related side effects were reported in 169, or 71%, of patients in the Lenvima plus Keytruda arm and 76, or 32%, of patients in the placebo arm, with the most common being hypertension (57, or 24%, versus 18, or 7%) and decreased platelet count (27, or 11%, versus 15, or 6%).
It was noted in the study that deaths due to treatment-related side effects occurred in four patients in the Lenvima plus Keytruda arm — with one case each of hepatic failure, gastrointestinal hemorrhage, myositis and immune-mediated hepatitis — and one patient in the placebo group, due to brain stem hemorrhage.
Reference:
“Transarterial chemoembolisation combined with lenvatinib plus pembrolizumab versus dual placebo for unresectable, non-metastatic hepatocellular carcinoma (LEAP-012): a multicentre, randomised, double-blind, phase 3 study” by Dr. Masatoshi Kudo et al., The Lancet.
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