Dr. Ahn on the Evolution of First-line Treatment Options in HCC

Daniel H. Ahn, DO, oncologist, internist, and assistant professor of medicine, Mayo Clinic, discusses the evolution of first-line treatments in advanced hepatocellular carcinoma (HCC).

Prior to advancements in the use of immunotherapy, oral TKIs were the primary option for HCC in the frontline, Ahn begins. The TKI sorafenib (Nexavar) remained the standard of care (SOC) in this setting for several years, followed by lenvatinib (Lenvima), Ahn expands. However, early phase data from the phase 1/2 CheckMate-040 trial (NCT01658878) demonstrated the potential benefit of immunotherapy in the advanced refractory setting, he says. The study evaluated the safety, activity, and tolerability of nivolumab (Opdivo) alone or in combination with ipilimumab (Yervoy) and cabozantinib (Cabometyx) vs sorafenib. Initial results showed that nivolumab plus ipilimumab had a manageable safety profile, promising objective response rate, and durable responses, Ahn reports.

Based on these data, the potential use of immunotherapy was evaluated in the first-line setting, Ahn continues. The phase 3 CheckMate-459 trial (NCT02576509) compared the effect of nivolumab vs sorafenib on patient survival in this setting. The trial did show a numerical improvement in overall survial (OS), but this result was not statistically significant, Ahn qualifies. Although this was a negative trial, the study did indicate the need for continued investigation of these agents, Ahn notes. To maximize benefit from PD-1 inhibitors, the focus of continued research shifted to PD-L1 inhibitors combined with other treatment options, including antiangiogenic therapies, Ahn states.

Accordingly, the phase 3 IMBrave150 trial (NCT03434379) was designed to evaluate the ICIcombination of atezolizumab (Tecentriq) and bevacizumab (Avastin) in previously untreated HCC, Ahn explains. The trial was positive, and demonstrated improved OS and progression-free survival (PFS) with the combination compared with sorafenib. Based on these findings, the regimen gained FDA approval on May 29, 2020.

The phase 3 HIMALAYA trial (NCT03298451) in unresectable HCC also reported positive results with the STRIDE regimen of durvalumab (Imfinzi) and tremelimumab (Imjudo), Ahn states. In this trial, the PD-L1 and CTLA-4 inhibitor combination demonstrated an improvement in OS vs sorafenib. Similarly, the regimen gained FDA approval on October 24, 2022, in accordance with these results.

These regimens have become SOC options in the first line for patients with advanced or unresectable HCC without immunotherapy contraindications, Ahn concludes.

Editor’s Note: This interview was conducted prior to the 2023 ASCO Gastrointestinal Cancers Symposium.