Imjudo-Imfinzi Regimen Improves Survival With Manageable Side Effects in Liver Cancer Subset

Patients with unresectable hepatocellular carcinoma, a type of liver cancer, treated with a single dose of Imjudo (tremelimumab) followed by regular intervals of Imfinzi (durvalumab) — the STRIDE regimen — experienced manageable mild to moderate immune-related side effects, according to findings from a recent trial.

Results from the phase 3 HIMALAYA trial were presented during the 2023 American Society of Clinical Oncology Annual Meeting.

In addition, those who developed immune-related side effects had improvements in overall survival (the time from treatment when a patient with cancer is still alive). The median overall survival after developing an immune-related side effect was 23.2 months versus 14.1 months among those who did not.

More specifically, the six-months overall survival rates between those who did, and those who did not, experience an immune-related side effect, respectively, were 81.3% versus 77.1%. The 12-month overall survival rates were 69.1% versus 55.2%; the 24-month overall survival rates were 48.9% versus 35.3%; and the 36-months overall survival rates were 36.2% versus 27.7%, respectively.

At 36 months, the overall survival rates were higher among those receiving STRIDE than those receiving Nexavar (sorafenib), regardless of immune-related side effect development. In the trial population, the 36-month overall survival rate with STRIDE (393 patients) was 30.7 months and with Nexavar (389 patients), the rate was 20.2%.

Moreover, in assessing only patients who received STRIDE, the median overall survival among those who developed an immune-related side effect (139 patients) was 36.2 months, and the median overall survival among those with no immune-related side effect (249 patients) was 27.7 months.

The findings also demonstrated that the overall survival benefit was similar for patients receiving Imfinzi monotherapy regardless of immune-related side effect development. The median overall survival for those in this group who developed an immune-related side effect was 17.8 months and the median overall survival for those who did not develop an immune-related side effect was 16.5 months.

Among patients who received Imfinzi as monotherapy, the six-month overall survival rates between those who did, and did not, experience an immune-related side effect, respectively, were 82.8% versus 71.8%. The rates for 12-month overall survival, respectively, were 60.9% versus 58.2%. The 24-months overall survival rates were 39.1% versus 39.3% and the 36-month overall survival rates were 20.6% versus 25.7%, respectively.

The most common immune-related side effects to occur with STRIDE were hypothyroidism (10.1%), hyperthyroidism (4.7%), diarrhea (4.4%), rash (2.3%) and hepatitis (2.3%). Among those receiving Imfinzi monotherapy, the most common immune-related side effects included hypothyroidism (3.9%), increases in alanine transaminase, which can indicate liver disease (ALT; 3.6%), and increases in aspartate aminotransferase (AST; 3.6%). Most events occurred within the first three months of treatment.

“The occurrence of (immune-mediated side effects) did not preclude participants from experiencing an (overall survival) benefit with stride and long-term survival was observed with STRIDE, irrespective of (immune-mediated side effect) occurrence,” Dr. George Lau, chairman and senior consultant in gastroenterology and hepatology at the Humanity & Health Medical Group in Hong Kong, said in a presentation of the findings.

The STRIDE regimen was assessed against Nexavar in the phase 3 HIMALAYA study — the results of which demonstrated that patients with unresectable hepatocellular carcinoma achieved superior survival with the experimental regimen and experienced a manageable safety profile.

The trial enrolled adults with unresectable hepatocellular carcinoma who were not eligible for locoregional therapy. These patients did not receive prior systemic therapy.

They were randomly assigned to received either STRIDE (393 patients), which consisted of Imjudo plus Imfinzi; Imfinzi alone (389 patients); or Nexavar (389 patients) every day.

Researchers focused on several factors including overall survival, safety, progression-free survival (the time during and after treatment when a patient with cancer lives with the disease without worsening), objective response rate (percentage of patients with a partial or complete response to treatment) and disease control rate (percentage of patients whose disease shrinks or stabilizes from treatment).

Treatment-Related Questions in Unresectable Hepatocellular Carcinoma

In a post-abstract presentation discussion, Dr. Namrata Vijayvergia, agreed with Lau that the STRIDE regimen has presented itself as a reasonable frontline option for this patient population. However, according to Vijayvergia, who is assistant chief of gastrointestinal medical oncology at Fox Chase Cancer Center in Philadelphia, treatment selection will still be largely dependent on the differential toxicities between the different treatment options, and patient wishes.

She also pointed out that data comparing the different options’ cost effectiveness are necessary in providing a comprehensive picture of current treatment options in unresectable hepatocellular carcinoma.

“It is a discussion we need to have with our patients,” she said. “We also need some data on the cost effectiveness of this new regimen because both (Imfinzi) and (Imjudo) are not cheap.”

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