Anti-TIGIT Shows Promise in Unresectable Liver Cancer

The randomized phase Ib-II MORPHEUS-Liver study showed that adding the anti-TIG monoclonal antibody tiragolumab to standard first-line treatment resulted in better response rates and improved survival for patients with unresectable HCC.

At clinical deadline, the 41 patients assigned to treatment with tiragolumab had a confirmed objective response rate of 43% compared with 11% among the 18 patients who received the standard regimen of atezolizumab (Tecentriq) and bevacizumab (Avastin) alone, Richard said. S. Finn, MD, of the University of California, Los Angeles, and colleagues.

In addition, median progression-free survival (PFS) was 12.3 months in the tiragolumab group compared with 4.2 months in the control group (HR 0.51, 95% CI 0.27-0.95), with higher rates of PFS. Progression in the tiragolumab group at 6 months. (75% vs. 41%) and 12 months (50% vs. 24%).

Median overall survival was 28.9 months in the tiragolumab group compared with 15.1 months in the control group (HR 0.39, 95% CI 0.19-0.78).

“To our knowledge, our study represents the first global, randomized study to report data on an anti-TIGIT monoclonal antibody in HCC,” Finn and colleagues wrote in a study. Lancet OncologyAdding that the study results indicate that tiragolumab in combination with atezolizumab and bevacizumab “could represent a promising new first-line treatment option” in unresectable disease.

In a Comment accompanying the studyDual immune checkpoint inhibitor regimens based on CTLA-4 antagonists “have revolutionized the treatment paradigm by allowing a significant portion of patients to achieve long-term disease control and remission,” noted Thomas Yao, MD, of the University of Hong Kong, and colleagues. . survival.”

“We are keen to see whether the apparent increase in objective response rate in the tiragolumab plus atezolizumab and bevacizumab group could ultimately translate into long-term survival benefits,” they added.

Explaining the rationale behind the study, Finn and colleagues said that while PD-L1 and VEGF blockade using atezolizumab plus bevacizumab has been shown to improve survival in unresectable stage III hepatocellular carcinoma, IMbrave150 experiencethe median overall survival remains less than two years, “highlighting the ongoing unmet medical need for more effective first-line regimens to help improve patient outcomes in unresectable hepatocellular carcinoma.”

the Study of liver morpheus It was performed at 26 centers across China, France, Israel, New Zealand, South Korea, and the United States from August 2020 to February 2022 and included 59 patients with previously untreated resectable, locally advanced HCC, and an Eastern Cooperative Oncology Group performance status of 0. – 1, life expectancy is not less than 3 months. The median age was 65 years, 79% were men, and most patients were either Asian (40%) or white (36%).

Some notable adverse events were more common in the tiragolumab group than in the control group, including pruritus (50% vs. 17%), joint pain (33% vs. 11%), and diarrhea (30% vs. 6%), although these The events were mainly grade 1-2.

The most common grade 3-4 adverse events were hypertension (15% in the tiragolumab group vs. 11% in the control group), aspartate aminotransferase (8% vs. 6%), and proteinuria (5% vs. 11%).

Serious adverse events occurred in 53% of patients in the tiragolumab group and 56% of patients in the atezolizumab-bevacizumab group, and serious treatment-related adverse events occurred in 25% and 28%, respectively. Treatment-related deaths occurred in one patient in the tiragolumab group (due to cholestasis) and two patients in the control group (due to esophageal variceal bleeding and upper gastrointestinal bleeding).

Yao and his colleagues said that while the study results were “undoubtedly exciting,” they noted that they were small, with only 18 patients in the control group. This “may have contributed to the lower objective response rate observed,” they suggested, noting that the response rate was lower than that seen with atezolizumab and bevacizumab in the IMbrave150 or phase Ib trial. Trial GO30140.

They also noted that the rates of serious adverse events and rates of treatment-related serious adverse events were “somewhat unexpected,” given the fact that this was an early-stage study, and that atezolizumab plus bevacizumab had an all-cause serious adverse event rate that was lower in the IMbrave150 trial. The rate of treatment-related adverse events was less severe in the GO30140 trial.

“Whether the three-drug combination will lead to unacceptably high toxicity in the broader population is an important question to answer in the ongoing phase III trial. Experiment IMbrave152/SKYSCRAPER-14“, they suggested.