STRIDE gave acceptable toxicity in poor-prognosis HCC usually excluded from trials, with modest response

Design

Phase 3b, single-arm, multicohort study (SIERRA)

Population

111 adults with unresectable HCC and Child-Pugh B7/B8, ECOG PS 2 or main portal vein thrombosis

Primary outcome

Grade 3 or 4 possibly related adverse events within 6 months; objective response

Effect

Grade 3/4 events 19.8% (95% CI 12.9% to 28.5%); response 14.4% (8.5% to 22.4%)

Up to 65% of patients with unresectable hepatocellular carcinoma in practice have features that exclude them from phase 3 trials: Child-Pugh B liver function, poorer performance status or main portal vein tumour thrombosis. SIERRA, a phase 3b single-arm study, gave these patients the STRIDE regimen (one dose of tremelimumab 300 mg plus durvalumab 1500 mg, then durvalumab every four weeks).

Of 111 participants (44 Child-Pugh B7/B8, 47 ECOG performance status 2, 20 with main portal vein thrombosis), 19.8% had grade 3 or 4 possibly treatment-related adverse events within six months (95% CI 12.9% to 28.5%), with similar rates across cohorts. Objective response was 14.4% overall: 6.8% in Child-Pugh B, 21.3% with performance status 2 and 15.0% with portal vein thrombosis.

The practical value is that it gives clinicians prospective safety data for patients they already see and often treat off-trial. Toxicity looked manageable. Response in Child-Pugh B was low, and there is no comparator, so this cannot show survival benefit. Decisions for these patients still rest on liver reserve and individual goals.

• Consider STRIDE for selected patients with Child-Pugh B7/B8 or performance status 2 after multidisciplinary discussion.
• Expect lower response in Child-Pugh B liver function and discuss this frankly.
• Monitor liver function closely, as immune-related hepatitis can be hard to separate from decompensation.
• Weigh treatment against best supportive care, given the absence of a comparator arm.

Why it matters

It is prospective safety data for the majority of real-world patients that phase 3 trials leave out.

Don't overread it

Single-arm with no survival comparison; it does not show STRIDE extends life in this group.

The statistics, in plain English

Single-arm results describe what happened, not what would have happened without treatment. The response of 6.8% in Child-Pugh B has a wide interval (1.4% to 18.7%) because the cohort was small.

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