- Design
- Phase 3b, single-arm study (SIERRA)
- Population
- 111 patients with unresectable HCC and Child-Pugh B7 to B8, ECOG 2 or main portal vein thrombosis
- Primary outcome
- Grade 3 or 4 treatment-related adverse events within 6 months, and objective response
- Effect
- Toxicity 19.8% (12.9 to 28.5); response 14.4% (8.5 to 22.4)
SIERRA enrolled patients with unresectable hepatocellular carcinoma who had poor prognostic features usually excluded from trials: Child-Pugh B7 or B8 liver function, ECOG performance status 2, or tumour thrombus in the main portal vein. All received the STRIDE regimen.
Serious treatment-related toxicity occurred in about one in five, similar to trials in fitter patients. Responses were less frequent, particularly with impaired liver function.
The study shows the regimen is tolerable in these groups. Whether it extends survival compared with best supportive care or other options is unknown.
- Grade 3 or 4 treatment-related adverse events within six months occurred in about 20%.
- Objective response was 14% overall.
- Response was lowest in Child-Pugh B7 to B8 (7%) and highest with performance status 2 (21%).
- Patients with main portal vein thrombosis had 15% response.
- Weigh liver reserve and goals of care before starting immunotherapy in these groups.
Why it matters
Most patients seen in practice would have been excluded from the pivotal trials, and this gives the first prospective safety data in them.
Don't overread it
A single-arm study without a control group cannot show a survival benefit.
The statistics, in plain English
With 20 to 47 patients per group, the subgroup intervals are wide; the Child-Pugh B response could be anywhere from about 1% to 19%.
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