RATIONALE-208 subanalyses boost tislelizumab potential for HCC

The monoclonal antibody tislelizumab continued to show promise as a treatment alternative in certain subgroups of patients with previously treated advanced hepatocellular carcinoma (HCC), according to subgroup analyses of the phase II, single-arm RATIONALE-208 study.

 

According to previous systemic therapy

This subanalysis sought to evaluate whether the clinical activity of tislelizumab varied based on the number of prior lines (PL) of systemic therapy. Of the 249 participants enrolled (median age 62 years, 87 percent male), 138 had received one PL (1PL subgroup) of systemic therapy while the rest had ≥2 PL (≥2PL subgroup). [ESMO WCGI 2022, abstract P-19]

At data cutoff, median follow-up for the respective 1PL and ≥2PL subgroups were 13.3 and 11.9 months.

There were no differences between the two subgroups evaluated, be it in terms of independent review committee (IRC)-assessed objective response rate (13.0 percent vs 12.6 percent), median overall survival (OS; 13.8 vs 12.4 months), median progression-free survival (PFS; 2.6 vs 2.7 months), and median durations of response (DoR; not reached in both subgroups).

Median durations of exposure were also similar in both the 1PL and ≥2PL subgroups at 4.2 and 4.1 months, respectively.

Among responders (n=18 [1PL] and 14 [≥2PL]), responses were ongoing in six and two participants, respectively.

“[In our study,] tislelizumab demonstrated durable antitumour activity regardless of the number of PL of systemic therapy in … patients with previously treated advanced HCC,” said the researchers.

 

Chinese subpopulation

When comparing the Chinese subpopulation (ie, from Mainland/Taiwan China; n=122; median age 58 years, 88 percent male) against the overall cohort, no differences were observed between arms in terms of IRC-assessed antitumour activity (12.3 percent vs 12.9 percent), median OS (13.7 vs 13.2 months), and median PFS (1.4 vs 2.7 months). Median DoR was also not reached in either cohort. [ESMO WCGI 2022, abstract P-25]

Median follow-up was about 13 months in both the Chinese and overall populations at data cutoff. Median durations of tislelizumab exposure were 2.8 and 4.1 months, respectively.

Eight out of the 32 responders in the overall cohort had ongoing responses, but there were none from the 15 responders in the Chinese cohort.

The main difference observed in the study was HCC aetiology. About 90 percent of participants in the Chinese population had HCC caused by hepatitis B only, while half of the cases in the overall cohort were attributable to hepatitis B.

“[O]ver 50 percent of HCC cases worldwide occur in China,” the researchers noted. [J Hepatol 2020;72:250-261] “[Our findings showed that] tislelizumab had durable antitumour activity in Chinese patients with previously treated advanced HCC.”

 

Augments primary findings

Taken together, these findings reinforce the results of the primary analysis showing encouraging and durable clinical activity and favourable tolerability in the overall population.

Overall, tislelizumab was well-tolerated and had generally similar rates of treatment-emergent and treatment-related adverse events (AEs) regardless of the number of PL of therapy. The AE rates were also similar in the comparison between the Chinese and overall populations. “[T]he safety profile was consistent with the established profile of PD-1/PD-L1 inhibitors,” said the researchers. [Lancet Oncol 2018;19:940-952; Lancet 2017;389:2492-2502]

The ongoing phase III RATIONALE-301 study comparing tislelizumab against sorafenib shall give further insight into the potential of tislelizumab as a first-line treatment alternative in adult patients with advanced HCC. [Future Oncol 2019;15:1811-1822]