STRIDE regimen boosts OS in unresectable HCC

The addition of tremelimumab to durvalumab (STRIDE regimen) in the first-line setting improved overall survival (OS) compared with sorafenib in patients with advanced unresectable hepatocellular carcinoma (HCC), according to results of the phase III HIMALAYA trial.

“HIMALAYA met its primary endpoint [demonstrating] T300+D* was superior to sorafenib for OS,” said study author Dr Ghassan K. Abou-Alfa from the Memorial Sloan Kettering Cancer Center, New York, US.

“The STRIDE [T300+D] regimen and durvalumab monotherapy may represent new treatment options for patients with unresectable HCC,” he added.

The population of this global, open-label trial comprised 1,171 patients with unresectable HCC, BCLC** stage B or C, and ECOG performance status 0–1 with no prior exposure to systemic therapy and no main portal vein thrombosis. They were randomized to receive T300+D, durvalumab 1,500 mg Q4W, or sorafenib 400 mg BID, with durvalumab and sorafenib continued until disease progression.

After a median follow-up of 33.18 and 32.23 months for T300+D and sorafenib, respectively, OS was significantly improved with T300+D compared with sorafenib (median 16.4 vs 13.8 months; hazard ratio [HR], 0.78, 96.02 percent confidence interval [CI], 0.65–0.92; p=0.0035). At 18 months, the OS rate was 48.7 percent vs 41.5 percent and at 36 months, 30.7 percent vs 20.2 percent. [ASCO GI 2022, abstract 379]

After a median follow-up of 32.56 and 32.23 months for durvalumab and sorafenib, respectively, OS with durvalumab monotherapy was non-inferior to sorafenib (median 16.6 vs 13.8 months; HR, 0.86, 95.67 percent CI, 0.73–1.03), with 18- and 36-month OS of 47.4 percent vs 41.5 percent and 24.7 percent vs 20.2 percent, respectively.

Progression-free survival (PFS) was comparable between the T300+D, durvalumab, and sorafenib arms (median 3.78, 3.65, and 4.07 months, respectively; HR, 0.90, 95 percent CI, 0.77–1.05 [T300+D] and HR, 1.02, 95 percent CI, 0.88–1.19 [durvalumab] vs sorafenib). Median time to progression was 5.42, 3.75, and 5.55 months, respectively, and 12.5, 8.2, and 4.9 percent, respectively, remained progression free at data cut-off.

Objective response rate was 20.1, 17.0, and 5.1 percent in the T300+D, durvalumab, and sorafenib arms, respectively, with 12, 6, and 0 patients, respectively, achieving complete response, and 67, 60, and 20 partial response. The median duration of response was 22.34, 16.82, and 18.43 months, respectively, with 65.8, 57.8, and 63.2 percent remaining in response at 12 months.

Treatment-related adverse events (TRAEs) occurred in 75.8, 52.1, and 84.8 percent of T300+D, durvalumab, and sorafenib recipients, respectively, with 25.8, 12.9, and 36.9 percent grade 3–4 TRAEs, and 17.5, 8.2, and 9.4 percent serious AEs. TRAEs led to discontinuation in 8.2, 4.1, and 11.0 percent, respectively, and to death in nine T300+D and three sorafenib recipients.

Grade ≥3 hepatic TRAEs*** occurred in 7.0, 5.2, and 4.8 percent of T300+D, durvalumab, and sorafenib recipients, respectively. Grade ≥3 haemorrhage** incidence was low, occurring in two T300+D and six sorafenib recipients. Grade 3–4 immune-mediated AEs occurred in 12.6 and 6.4 percent of T300+D and durvalumab recipients, respectively.

“STRIDE [T300+D] appeared to provide a long-term survival benefit, with a landmark 36-month OS of 30.7 percent,” remarked Abou-Alfa. “Both STRIDE and durvalumab monotherapy had manageable safety profiles with … no increase in liver toxicity or bleeding risk.”

“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 noted.

“HIMALAYA chose a novel approach of priming with a single dose of combination immunotherapy followed by the single agent durvalumab,” mentioned Professor Cathy Eng, ASCO Expert in gastrointestinal cancers, who was not affiliated with the study.

“While the primary endpoint was met, based on the current data … PFS was not superior in either investigational arm relative to the control arm, requiring further discussion,” she said.