Author: By Laura Cowen, medwireNews Reporter
medwireNews: Treatment with the novel combined immunotherapy regimen STRIDE (Single Tremelimumab Regular Interval Durvalumab) significantly improves overall survival (OS) relative to sorafenib in people with unresectable hepatocellular carcinoma (HCC), results of the HIMALAYA trial show.
The findings, presented at the 2022 ASCO Gastrointestinal Cancers Symposium in San Francisco, California, USA, could “represent new treatment options for patients with unresectable HCC”, lead author Ghassan Abou-Alfa, from the Memorial Sloan Kettering Cancer Center in New York, USA, told delegates.
The international phase III study included 1171 patients with unresectable HCC who had not previously received systemic therapy.
They were randomly assigned to receive treatment with the STRIDE regimen, which involved a priming dose of tremelimumab 300 mg plus durvalumab 1500 mg followed by durvalumab 1500 mg every 4 weeks, or they were given monotherapy with durvalumab 1500 mg every 4 weeks or sorafenib 400 mg twice daily.
An additional 153 patients were randomly assigned to receive tremelimumab 75 mg every 4 weeks for four doses plus durvalumab 1500 mg every 4 weeks until disease progression. However, this arm was closed early following a preplanned analysis of a phase II study that showed no meaningful difference relative to durvalumab. The results from this arm were not presented at the meeting.
Ghassan Abou-Alfa reported that median OS was 16.4 months among the 393 participants who received STRIDE, 16.6 months in the 389 given durvalumab monotherapy and 13.8 months in the 389 individuals who received sorafenib. Corresponding 36-month survival rates were 30.7%, 24.7% and 20.2%.
At the time of data cutoff, the risk for death was a significant 22% lower with STRIDE than with sorafenib, meeting the primary objective of the study. The secondary objective – noninferior OS for with durvalumab versus sorafenib – was also met.
There was no significant difference in median progression-free survival among the three arms, at 3.8, 3.7 and 4.1 months for STRIDE, durvalumab and sorafenib, respectively, but the objective response rates were higher for STRIDE (20.1%) and durvalumab (17.0%) than for sorafenib (5.1%).
In addition, Ghassan Abou-Alfa said that the median time to response was an “impressive” 2.2 months in the STRIDE arm and 2.1 months in the durvalumab arm, compared with 3.8 months in the sorafenib arm.
The presenter also noted that “safety and tolerability were as expected”. Approximately a quarter (25.8%) of individuals given STRIDE experienced a grade 3 or 4 treatment-related adverse event (TRAE) compared with 12.9% and 36.9% of those given durvalumab and sorafenib, respectively.
Grade 3–5 hepatic TRAE rates were 7.0%, 5.2%, and 4.8% for STRIDE, durvalumab and sorafenib, respectively, while haemorrhage of this severity occurred in a corresponding 0.5%, 0.0%, and 1.6% of patients and there were no cases of oesophageal varices haemorrhage.
However, discussant Anthony El-Khoueiry, from the USC Norris Comprehensive Cancer Center in Los Angeles, California, USA, pointed out that the study excluded patients with portal vein thrombosis, who are at the greatest risk of bleeding.
In spite of this, he said that a “single priming dose of tremelimumab results in a favorable risk-benefit ratio”, pointing out that only 20.1% of participants were given high-dose steroids to manage immune-mediated AEs, compared with 57.1% of participants given nivolumab plus ipilimumab in the CheckMate 040 trial.
The rates of grade 3 or worse immune-mediated AEs were 12.6% with STRIDE and 6.4% with durvalumab monotherapy. In all, 8.2% of participants discontinued STRIDE due to a TRAE compared with 4.1% of those given durvalumab and 11.0% of those who received sorafenib. TRAEs that led to death occurred in 2.3%, 0.0% and 0.8%, respectively.
After discussing the current possibilities for systemic treatment of unresectable HCC, Anthony El-Khoueiry concluded that “STRIDE with the combination of one priming dose with tremelimumab and regular interval durvalumab is a new first-line treatment option for advanced HCC patients”.
He added that it may be “the preferred regimen for patients who have bevacizumab contraindications, high bleeding risk, or cannot get an endoscopy within 6 months of treatment.”
Abou-Alfa GK, Chan SL, Kudo M, et al. Phase 3 randomized, open-label, multicenter study of tremelimumab (T) and durvalumab (D) as first-line therapy in patients (pts) with unresectable hepatocellular carcinoma (uHCC): HIMALAYA. J Clin Oncol 2022;40(4_suppl):379–379. DOI: 10.1200/JCO.2022.40.4_suppl.379
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