Dr. Kim on The Evaluation of TKI/Immunotherapy Combos in HCC

Richard Kim, MD, professor, Moffitt Cancer Center, discusses the evaluation of TKI and immunotherapy combination regimens in hepatocellular carcinoma (HCC).

The phase 3 LEAP-002 trial (NCT03713593) of lenvatinib (Lenvima) plus pembrolizumab (Keytruda) failed to meet the coprimary end points of progression-free survival (PFS) and overall survival (OS) vs lenvatinib plus placebo, Kim says. The phase 3 COSMIC-312 trial (NCT03755791) that examined cabozantinib (Cabometyx) plus atezolizumab (Tecentriq) met a coprimary end point of PFS; however, it missed the coprimary end point of OS, Kim adds. Although TKI/immunotherapy combinations failed to meet all their primary objectives in these 2 trials, there are some nuances for comparing these data with traditional immunotherapy/VEGF inhibitor combinations, according to Kim.

For example, LEAP-002 used single-agent lenvatinib in its control arm, and those patients who received the TKI alone did well, Kim says. If the trial investigated lenvatinib plus pembrolizumab vs sorafenib (Nexavar) in the control arm, it is possible that it would have been a positive study, according to Kim.

Another phase 3 study (NCT03764293) examined the combination of the TKI rivoceranib and the checkpoint inhibitor camrelizumab vs sorafenib alone. The doublet provided improvements in PFS and OS in patients with unresectable HCC, Kim concludes.