STRIDE regimen benefit in unresectable HCC consistent across baseline liver function

The overall survival (OS) benefit observed with the STRIDE regimen compared with sorafenib in patients with unresectable hepatocellular carcinoma (HCC) is consistent regardless of baseline liver function, according to exploratory analysis of data from the phase III HIMALAYA trial presented at ESMO GI 2022.

Participants were 1,171 adults with unresectable HCC, Child-Pugh class A, BCLC* stage B or C, and ECOG performance score of 0–1 with no prior exposure to systemic therapy or main portal vein thrombosis. They were randomized 1:1:1 to receive one dose of tremelimumab 300 mg plus durvalumab 1,500 mg Q4W (T300+D; STRIDE regimen), durvalumab 1,500 mg Q4W monotherapy, or sorafenib 400 mg BID.

Mean Child-Pugh score at baseline was 5.3, with a majority of patients (71–75 percent) having Child-Pugh A/5. Most patients had an albumin-bilirubin (ALBI) grade of 1 (52.8 percent) or 2/3 (47.1 percent).

Previously published results showed an improvement in OS with T300+D compared with sorafenib (median 16.43 vs 13.77 months; hazard ratio [HR], 0.78, 96.02 percent confidence interval [CI], 0.65–0.93; p=0.0035). [NEJM Evid 2022;doi:10.1056/EVIDoa2100070]

The present analysis demonstrated that the OS improvement with T300+D over sorafenib was consistent in patients with ALBI grade 1 (median 23.43 vs 19.02 months; HR, 0.79, 95 percent CI, 0.62–1.01) and ALBI grade 2/3 (median 11.30 vs 9.72; HR, 0.83, 95 percent CI, 0.65–1.05). [ESMO GI 2022, abstract O-5]

The OS outcomes observed with durvalumab monotherapy vs sorafenib in the overall population (median 16.6 vs 13.8 months; HR, 0.86, 95.67 percent CI, 0.73–1.03) were also consistent in patients with ALBI grade 1 (median 21.16 vs 19.02; HR, 0.91, 95 percent CI, 0.71–1.15) and ALBI grade 2/3 (median 12.29 vs 9.72 months; HR, 0.87, 95 percent CI, 0.69–1.09).

“ALBI grade 1 was associated with longer survival than ALBI grade 2/3, regardless of treatment arm,” said study author Professor Arndt Vogel from the Hannover Medical School in Hannover, Germany.

Objective response rate (ORR) was greater with T300+D and durvalumab monotherapy compared with sorafenib in the overall population (20.1, 17.0, and 5.1 percent, respectively), as well as in patients with ALBI grade 1 (21.7, 18.7, and 7.4 percent, respectively) and ALBI grade 2/3 (18.3, 15.2, and 2.7 percent, respectively). Time to response was shorter in patients who received T300+D or durvalumab monotherapy vs sorafenib in the overall population (median 2.17, 2.09, and 3.78 months, respectively) and ALBI grade 2/3 (median 3.52, 3.65, and 9.10 months, respectively). Duration of response (DoR) with T300+D was consistent in the overall, ALBI grade 1, and ALBI grade 2/3 populations (median 22.34, 22.34, and 26.55 months, respectively), with a greater DoR with T300+D over durvalumab monotherapy or sorafenib in the ALBI grade 2/3 population (median 26.55, 13.83, and 12.25 months, respectively).

Grade 3–4 treatment-emergent adverse events (TEAEs) occurred at a comparable rate between T300+D and sorafenib recipients across the overall (50.5 percent vs 52.4 percent), ALBI grade 1 (51.4 percent vs 51.8 percent), and ALBI grade 2/3 populations (49.7 percent vs 53.1 percent). Serious TEAEs occurred in 40.5 percent vs 29.7 percent, 41.2 percent vs 24.9 percent, and 39.8 percent vs 35.0 percent, respectively. TEAEs led to discontinuation in 13.7 percent vs 16.8 percent, 12.5 percent vs 10.2 percent, and 15.2 percent vs 24.3 percent, respectively, and to death in 7.7 percent vs 7.2 percent, 3.7 percent vs 5.6 percent, and 12.9 percent vs 9.0 percent, respectively. Immune-mediated TEAEs occurred in 35.8 percent vs 8.0 percent, 43.5 percent vs 10.2 percent, and 26.3 percent vs 5.6 percent, respectively.

“Safety in both ALBI subgroups was generally consistent with the full analysis set for both T300+D and durvalumab recipients,” said Vogel. Among durvalumab recipients, serious TEAEs occurred in 29.6, 24.2, and 35.3 percent in the overall, ALBI grade 1, and ALBI grade 2/3 populations, respectively. Immune-mediated TEAEs occurred in 16.5, 12.6, and 20.5 percent, respectively.

Among patients who remained in the study, liver function remained stable over time among patients assigned to T300+D or durvalumab.

“The STRIDE (T300+D) regimen and durvalumab monotherapy showed favourable benefit-risk profiles compared with sorafenib, irrespective of baseline ALBI grade,” remarked Vogel.

“These results support the use of the STRIDE regimen as a new treatment option in patients with unresectable HCC,” he concluded.