Five-year overall survival (OS) and OS by baseline liver function from the Phase 3 HIMALAYA study of tremelimumab (T) plus durvalumab (D) in unresectable hepatocellular carcinoma (uHCC)

Background: In the Phase 3 HIMALAYA study (NCT03298451) in uHCC, STRIDE (Single T Regular Interval D) significantly improved OS versus sorafenib (S) in the primary analysis (Abou-Alfa et al. NEJM Evid 2022) and demonstrated durable long-term survival with a 4-year OS rate of 25.2% (Sangro et al. Ann Oncol 2024). Albumin-bilirubin (ALBI) grade is an objective measure of liver function in HCC. Here, we report a 5-year OS analysis in uHCC and evaluate OS by baseline ALBI grade.

Methods: Participants (pts) were randomised to STRIDE, D or S. OS, the proportion of extended long-term survivors (eLTS; alive≥48 months) and serious adverse events (SAEs) were assessed in all pts or in subgroups of pts stratified by baseline ALBI grade (1 [score≤-2.60] vs 2/3 [score>-2.60 to≤-1.39/score>-1.39]). The data cut-off was 1 March 2024.

Results: The OS hazard ratio (HR) for STRIDE versus S was 0.76 (95% CI, 0.65–0.89; [Table 1]). The 5-year OS rate was 19.6% with STRIDE versus 9.4% with S (rate ratio, 2.09). In ALBI grade 1 pts, OS HR was 0.79 (95% CI, 0.63–0.99) for STRIDE versus S, and the 5-year OS rate was 24.3% with STRIDE versus 13.6% with S. In ALBI grade 2/3 pts, OS HR was 0.79 (95% CI, 0.63–1.00) for STRIDE versus S, and the 5-year OS rate was 13.7% with STRIDE versus 4.7% with S. Data for D are shown in the Table. In ALBI grade 1 versus 2/3 pts, 57/217 (26.3%) versus 26/175 (14.9%) were eLTS with STRIDE, and 36/203 (17.7%) versus 9/186 (4.8%) were eLTS with S. Rates of treatment-related SAEs with STRIDE did not change from the primary analysis for either ALBI subgroup ([Table 1]).

Table 1 

	All pts			ALBI grade 1			ALBI grade 2/3
	STRIDE (n=393)	D (n=389)	S (n=389)	STRIDE (n=217)*	D (n=198)	S (n=203)	STRIDE (n=175)*	D (n=191)	S (n=186)
OS HR (95% CI)	0.76 (0.65–0.89)	0.85 (0.73–1.00)	–	0.79 (0.63–0.99)	0.93 (0.74–1.16)	–	0.79 (0.63–1.00)	0.82 (0.65–1.02)	–
OS rates,%
48 months	25.2	19.0	15.1	31.9	20.7	22.1	17.1	17.3	7.1
60 months	19.6	14.4	9.4	24.3	15.5	13.6	13.7	13.2	4.7
Treatment-related SAEs, n/N (%)	68/388 (17.5)	33/388 (8.5)	37/374 (9.9)	44/216 (20.4)	14/198 (7.1)	16/197 (8.1)	24/171 (14.0)	19/190 (10.0)	21/177 (11.9)

*ALBI grade data not available for one pt.

Conclusions: STRIDE demonstrated an unprecedented 5-year survival rate, with no additional serious safety events observed, and long-term OS benefit over S in a diverse population of pts with uHCC regardless of baseline liver function. These results set a new benchmark in uHCC, with one in five pts alive with STRIDE at 5 years.

Clinical Trial identification: NCT03298451

Funding: AstraZeneca

Acknowledgements: Medical writing support, under the direction of the authors, was provided by Jennifer Stewart, PhD, MBA, on behalf of CMC Connect, a division of IPG Health Medical Communications, and was funded by AstraZeneca, in accordance with Good Publication Practice (GPP 2022) guidelines.

Previously presented at ESMO ASIA 2024, 127O, Masatoshi Kudo et al. – Reused with permission

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Artikel online veröffentlicht:
04. September 2025