Overcoming Resistance to Immune Checkpoint Blockade in Liver Cancer with Combination Therapy: Stronger Together?

A follow-up analysis in 2022 even updated the ORR to 18.3% and the mOS to 13.2 months. 43 Following these encouraging results, the randomized, double-blinded phase III trial KEYNOTE-240 ( Table 1 ) tested pembrolizumab as second-line treatment and included 413 patients with advanced HCC who were previously treated with sorafenib in comparison to placebo. 21 Although the trial did not reach statistical significance in 2019, the follow-up in 2020 showed an ORR of 18.3%, a mOS of 13.9 months, and a PFS of 3 months for pembrolizumab (placebo: ORR: 4.4%, mOS: 10.6 months, PFS: 2.8 months). 44 Similar results were shown by KEYNOTE-394 ( Table 1 ), which focused on a primarily Asian cohort. 45 The results were in line with KEYNOTE-240, showing comparable clinical activity and risk profile to other pembrolizumab studies. 19 21 43 44 There have been no large phase III trials investigating ICI monotherapy specifically in CCA.

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