FDA Approves Durvalumab in Combination with Tremelimumab for Unresectable HCC

The combination of durvalumab and tremelimumab has been approved for patients with unresectable hepatocellular carcinoma. The combination comes with warnings for immune-related adverse events and infusion reactions.

The FDA has approved a regimen of durvalumab (Imfinzi) plus tremelimumab (Imjudo) for the treatment of patients with unresectable hepatocellular carcinoma (HCC). The newly approved regimen—also known as the STRIDE regimen (single tremelimumab regular interval durvalumab)—will be administered as a single dose of tremelimumab at 300 mg in addition to 1500 mg of durvalumab, followed by durvalumab every 4 weeks.1

Positive findings from the phase 3 HIMALAYA trial (NCT03298451) supported the FDA’s decision. The findings demonstrated that patients who received the novel combination experienced a reduction in risk of death by 22% compared with patients who received sorafenib (Nexavar; HR, 0.78; 95% CI, 0.66-0.92; P = .0035). Moreover, at a 3-year follow-up, 31% of patients in the experimental arm were still alive vs 20% in the sorafenib arm. These findings were published in the New England Journal of Medicine.2

“Patients with unresectable liver cancer are in need of well-tolerated treatments that can meaningfully extend overall survival. 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,” lead study investigator Ghassan Abou-Alfa, MD, MBA, attending physician at Memorial Sloan Kettering Cancer Center, stated in a news release.1

HCC is the most common type of liver cancer and liver cancer is the third-leading cause of cancer deaths worldwide. It is also the sixth most reported cancer, and the rate of incidence is increasing—every year there are approximately 36,000 new diagnoses each year.

Because over half of patients with HCC receive their diagnosis at an advanced stage, there is an unmet need to expand treatment options foe this patient population. HIMALAYA was a randomized, open-label, multicenter, global trial, in which anti–CTLA-4 antibody, tremelimumab, was administered in combination, a PD-L1 blocking antibody.

The trial evaluated 1324 patients from across 16 different countries. The key end point was overall survival, and secondary end point included objective response rate and progression-free survival.

For safety, investigators found each agent to be consistent with previous reports, and no new safety signals were identified. Grade 3/4 treatment-emergent adverse events (AEs) occurred in 50.5% of patients who received the combination and 52.4% of patients receiving sorafenib.

Serious AEs related to treatment with the combination included hemorrhage (6%), diarrhea (4%), sepsis (2.1%), pneumonia (2.1%), rash (1.5%), vomiting (1.3%), acute kidney injury (1.3%), and anemia (1.3%). The most frequently reported AEs included rash, diarrhea, fatigue, pruritus, musculoskeletal pain, and abdominal pain.3

The combination may induce immune-related AEs and infusion reactions in patients. Patients should be educated on these potential AEs and taught to report and new or worsening symptoms.

“In the past, patients living with liver cancer had few treatment options and faced poor prognoses,” said Andrea Wilson Woods, president, and founder of Blue Faery: The Adrienne Wilson Liver Cancer Foundation, in the release.1 “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.”

References

  1. Imjudo (tremelimumab) in combination with Imfinzi approved in the US for patients with unresectable liver cancer. News release. AstraZeneca. October 24, 2022. Accessed October 24, 2022. https://bit.ly/3VUsQTw
  2. Abou-Alfa GK, Lau G, Kudo M, et al. Tremelimumab plus durvalumab in unresectable hepatocellular carcinoma. N Eng J Evid. 2022;1(8). doi:10.1056/EVIDoa2100070
  3. Imjudo (tremelimumab) in combination with Imfinzi approved in the US for patients with unresectable liver cancer. News release. Businesswire. October 24, 2022. Accessed October 24, 2022. https://bwnews.pr/3N0VQVV