Combination of Tremelimumab and Durvalumab Approved by FDA for Unresectable Liver Cancer

Today, FDA approved a dual immunotherapy option of tremelimumab, sold as Imjudo, in combination with durvalumab, sold as Imfinzi, for the treatment of adult patients with unresectable hepatocellular carcinoma (HCC), the most common type of liver cancer.

This regimen includes a single 300 mg dose of the anti-cytotoxic T lymphocyte–associated antigen 4 antibody tremelimumab added to a 1500 mg dose of the anti–programmed cell death ligand-1 antibody durvalumab, followed by a 1500 mg does of durvalumab every 4 weeks.

Approval is based on positive results from the phase 3 HIMALAYA trial, presented in June 2022 at the American Society of Clinical Oncology annual meeting. Results showed that patients taking the tremelimumab/durvalumab regimen experienced a 22% reduction in the risk of death compared with patients treated with sorafenib (HR, 0.78; 95% CI, 0.66-0.92 P = .0035).

Results appearing in NEJM Evidence showed that 31% of patients treated with the combination were still alive after 3 years, compared with 20% of patients treated with sorafenib at the point of follow-up.

Both therapies are made by AstraZeneca, which announced the approval in a statement.

Liver cancer, which is the sixth most commonly diagnosed cancer worldwide, is the fastest-rising cause of cancer death in the United States; an estimated 36,000 cases will be diagnosed in this country in 2022.

“Patients with unresectable liver cancer are in need of well-tolerated treatments that can meaningfully extend overall survival,” Ghassan Abou-Alfa, MD, MBA, attending physician at Memorial Sloan Kettering Cancer Center and principal investigator in HIMALAYA, said in a statement. “In addition to this regimen demonstrating a favorable 3-year survival rate in the HIMALAYA trial, safety data showed no increase in severe liver toxicity or bleeding risk for the combination, important factors for patients with liver cancer who also have advanced liver disease.”

Andrea Wilson Woods, president and founder for Blue Faery: The Adrienne Wilson Liver Cancer Foundation, said that previously, patients living with liver cancer had few treatment options.

“With this approval, we are grateful and optimistic for new, innovative, therapeutic options. These new treatments can improve long-term survival for those living with unresectable hepatocellular carcinoma, the most common form of liver cancer. We appreciate the patients, their families, and the broader liver cancer community who continue to fight for new treatments and advocate for others.”

The safety profiles of the combination of IMJUDO added to IMFINZI and for IMFINZI alone were consistent with the known profiles of each medicine, and no new safety signals were identified. The most common adverse events (AEs) among patients with unresectable HCC in the trial were rash, diarrhea, fatigue, pruritis, musculoskeletal pain, and abdominal pain; 41% of patients receiving the combination in HIMALAYA reported serious AEs.

Reference

Abou-Alfa GK, Lau G, Kudo M, et al. Tremelimumab plus durvalumab in unresectable hepatocellular carcinoma. NEJM Evid. 2022;1(8):doi:10.1056/EVIDoa2100070