The FDA has granted approval to tremelimumab (Imjudo®, AstraZeneca Pharmaceuticals) in combination with durvalumab for adult patients with unresectable hepatocellular carcinoma (uHCC).
"Patients with unresectable liver cancer are in need of well-tolerated treatments that can meaningfully extend overall survival," remarked Ghassan Abou-Alfa, MD, MBA, an Attending Physician at Memorial Sloan Kettering Cancer Center, and colleagues, regarding the HIMALAYA trial (NCT03298451), on which approval was based. "In addition to this regimen demonstrating a favorable three-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."
Safety and efficacy of tremelimumab in combination with durvalumab was assessed in a phase 3, multicenter, open-label trial, in which participating patients with confirmed uHCC, who had not received prior systemic treatment for HCC, were randomized to one of three arms. Patients in the first arm received a one-time dose of 300 mg of tremelimumab via intravenous (IV) infusion plus 1,500 mg of durvalumab via IV infusion on the same day, following by 1,500 mg of durvalumab IV every four weeks (STRIDE). Patients in the second arm received 1,500 mg of durvalumab IV every four weeks. Patients in the third arm received 400 mg of sorafenib orally twice daily. Each arm continued treatment until disease progression or unacceptable toxicity.
To assess the efficacy of tremelimumab plus durvalumab, the primary end point studied was overall survival, with key secondary end points being investigator-assessed progression-free survival and overall response rate according to RECIST v1.1. Overall survival was significantly improved for patients being treated with tremelimumab plus durvalumab with a median of 16.4 months, in comparison to those being treated with sorafenib, who had a median overall survival of 13.8 months. Median progression-free survival was 3.8 months in those receiving tremelimumab plus durvalumab and a median of 4.1 months for those receiving sorafenib. In addition, overall response rate for those receiving tremelimumab plus durvalumab was 20.1% compared with 5.1% for those receiving sorafenib.
The most common adverse events occurring in ≥20% of patients receiving tremelimumab plus durvalumab were rash, diarrhea, fatigue, pruritis, musculoskeletal pain, and abdominal pain.
"This regimen is the first combination of anti-PD-L1 and anti-CTLA4 antibodies for the treatment of HCC and has an acceptable and manageable toxicity profile", concluded Masatoshi Kudo, Professor and Chairman at the Department of Gastroenterology and Hepatology in the Kindai University School of Medicine, in his analysis of the HIMALAYA trial.
The recommended dosage for patients receiving tremelimumab who weigh 30 kg or more is 300 mg IV as a single dose plus 1,500 mg of durvalumab on Day 1 of Cycle 1, followed by 1500 mg of durvalumab via IV every four weeks. For patients weighing less than 30 kg, the recommended dosage is 4 mg/kg IV of tremelimumab as a single dose plus 20 mg/kg of durvalumab via IV, followed by 20 mg/kg of durvalumab via IV every 4 weeks.
For More Information
Abou-Alfa GK, Lau G, Kudo M, et al (2022). Tremelimumab plus durvalumab in unresectable hepatocellular carcinoma. NEJM Evidence, 1(8). DOI:10.1056/EVIDoa2100070
Clinicaltrials.gov (2022). Study of durvalumab and tremelimumab as first-line treatment in patients with advanced hepatocellular carcinoma (HIMALAYA). NLM identifier: NCT03298451.
Imjudo® (tremelimumab) prescribing information (2022). AstraZeneca Pharmaceuticals. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761289lbl.pdf
AstraZeneca (2022). Imjudo (tremelimumab) in combination with Imfinzi approved in the US for patients with unresectable liver cancer: press release. Available at: https://www.astrazeneca.com/media-centre/press-releases/2022/imfinzi-and-imjudo-approved-in-advanced-liver-cancer.html#!
US Food and Drug Administration (2022). FDA approves tremelimumab in combination with durvalumab for unresectable hepatocellular carcinoma. Available at: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-tremelimumab-combination-durvalumab-unresectable-hepatocellular-carcinoma?utm_medium=email&utm_source=govdelivery
Image credit: Ed Thuman. Licensed under CC BY 2.0
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