Initial uptake of durvalumab with or without tremelimumab for advanced hepatocellular carcinoma in routine clinical practice: Preliminary results of the international DT-real study

Background: HIMALAYA trial showed that durvalumab plus tremelimumab (Single Tremeli- mumab Regular Interval Durvalumab; STRIDE) significantly improved overall survival (OS) and that durvalumab (DUR) was non-inferior compared to sorafenib in patients with hepatocellular carcinoma (HCC). However, real world outcomes on this regimen have not been described. Methods: In the context of a prospectively maintained database including 953 patients (pts) with unresectable HCC treated with immunotherapy, we analysed a subgroup of pts treated with STRIDE or DUR across 5 centres in USA, Asia and Europe. We assessed OS, progression-free survival (PFS), objective response rate (ORR) by RECIST 1.1 (per investigator) and treatment- related adverse events (TRAEs) per CTCAE v.5.0. Results: Between February and May 2023, 59 pts initiated treatment with STRIDE or DUR (mean age 67.2 years, male sex 81.4%). 33 pts (55.9%) were treated in first-line (1L) and 26 (44.1%) in second- or further-line (.1L). STRIDE regimen was administered in 24 patients (40.7%): 6 pts in 1L, 18 pts in .1L. Child-Pugh class was A in 32 pts (54.2%), being more common in pts treated with STRIDE than DUR (79.2% vs 37.1%, p=0.003). ECOG-PS was 0 in 35 pts (59.3%) and it was more common in pts treated with STRIDE than DUR (79.2% vs 47.0%, p=0.015). Outcomes are reported in Table. After a median follow-up of 3.2 months (95%CI 2.6-3.8), median OS was not reached and 6-month OS rate was 59.4%. In pts treated with STRIDE, median OS was not reached and 6-month OS rate was 95.8%, while median OS was 4.9 months (95%CI 3.2-4.9) for DUR. Median PFS was 2.5 months (95% CI 1.9-3.8) and ORR (evaluable in 43 pts, 72.9%) was 16.3% (95%CI 6.5-33.5%). Any grade TRAEs and grade 3-4 TRAEs were 42.4% (95%CI 27.4-62.5) and 10.2% (95%CI 3.7-22.1%), respectively. TRAEs requiring systemic corticosteroid therapy occurred in 3 pts (5.1%). Conclusions: Preliminary observational data from DT-real confirm uptake of STRIDE and DUR across various lines of therapy, with encouraging efficacy and safety outcomes in routine practice.