The novel regimen, dubbed STRIDE (Single T Regular Interval D), comprised a single priming dose of the investigational agent tremelimumab followed by regular doses of durvalumab (Imfinzi).
Patients on this regimen experienced a 22% lower risk of death than patients treated with sorafenib (Nexavar), which at the time the trial began was the only approved frontline standard of care for patients with advanced HCC.
At 3 years, almost 31% of patients treated with combination therapy were still alive, versus 24.7% for durvalumab alone and 20.2% for sorafenib.
This novel regimen “may represent new treatment options for patients with untreated hepatocellular carcinoma,” said lead author Ghassan Abou-Alfa, MD, MBA, an attending physician at Memorial Sloan Kettering Comprehensive Cancer Center, New York. “Pending FDA approval, this novel dual immunotherapy regimen could be readily available to all patients and would not require additional safety assessments prior to treatment.”
He presented the new results here at the Gastrointestinal Cancers Symposium (GICS) 2022.
Discussing the abstract, Anthony B. El-Khoueiry, MD, from the University of Southern California, Norris Comprehensive Cancer Center, Los Angeles, agreed that the STRIDE regimen, with the combination of one priming dose of tremelimumab and regular interval durvalumab, is a new first-line treatment option for advanced HCC patients.
“But there are some limitations to the study and topics that will require further additional investigation,” he added.
Liver cancer increasing
Liver cancer is one of the few cancers for which deaths rates are increasing. In the United States. The overall rate of death due to liver cancer has doubled since 1980, Dr. Abou-Alfa told the audience. The most recent 5-year survival rates are 32.6% for localized disease, 10.8% with regional disease, and 2.4% with distant disease.
Until recently, first-line treatment for untreated HCC was limited to the multikinase inhibitors sorafenib and lenvatinib (Lenvima), which have been associated with median overall survival of approximately 1 year but also with toxicities that impact the quality of life, he commented.
“More recently, the anti-PD-L1 agent atezolizumab plus bevacizumab showed significant survival benefit versus sorafenib and have become a standard of care following approval in 2020,” Dr. Abou-Alfa said.
Tremelimumab is an experimental immunotherapy that targets the CTLA-4 receptor, and in 2020 it received orphan drug status for the treatment of HCC from the U.S. Food and Drug Administration. The authors hypothesized that tremelimumab would boost the response to durvalumab, a PDL-1 inhibitor, as this had been observed in the phase 2 Study 22 trial, which had tested the STRIDE regimen.
Now in the phase 3 HIMALAYA trial, the STRIDE regimen was compared to durvalumab used alone and to sorafenib used alone.
The trial randomized 1,171 patients to receive either the STRIDE regimen (a single dose of 75 mg tremelimumab plus 1,500 mg durvalumab every 4 weeks) or durvalumab alone (1,500 mg every 4 weeks) or sorafenib alone (400 mg twice daily).
Initially, there was also a lower-dose tremelimumab-containing arm, but recruitment into this arm was halted after a planned analysis of Study 22 failed to show a meaningful efficacy difference between that arm and durvalumab alone.
At data cutoff, the study’s primary objective was met. Overall survival was significantly improved for STRIDE versus sorafenib (hazard ratio; P = .0035). Median overall survival was 16.4 months for the STRIDE group versus 13.8 months for sorafenib and 16.6 months for durvalumab alone.
Median progression-free survival was 3.8 months, 3.7 months, and 41.1 months, respectively.
The overall response rate for the STRIDE arm was 20.1% compared to 17% for durvalumab, and 5.1% for sorafenib, and the median duration of response was 22.3 months, 16.8 months, and 18.4 months, respectively.
Treatment-related grade 3 or 4 adverse events occurred in 25.8% of patients on the combination, compared with 12.9% for durvalumab and 36.9% for sorafenib.
Grade 5 events occurred in 2.3% of the STRIDE group, compared with 0% among those receiving durvalumab alone and 0.8% in the sorafenib group. Treatment discontinuation due to events occurred in 8.2%, 4.1%, and 11.0% of patients, respectively.