Dr. Ahn on the Selection of First-line ICI-Based Combinations in HCC

Daniel H. Ahn, DO, oncologist, internist, and assistant professor of medicine, Mayo Clinic, discusses the importance of drug toxicity when selecting between first-line immune checkpoint inhibitor (ICI)–based regimens in hepatocellular carcinoma (HCC).

There are two main combination regimens currently available in the frontline setting for patients with HCC: atezolizumab (Tecentriq) plus bevacizumab (Avastin) and durvalumab (Imfinzi) plus tremelimumab (Imjudo). As there are no head-to-head efficacy data for these regimens, treatment selection should primarily be based on their respective safety profiles, Ahn explains.

Findings from the phase 3 IMBrave150 trial (NCT03434379) firmly established the combination of atezolizumab and bevacizumab as the standard of care in the first-line setting, and led to the regimen's approval on May 29, 2020. In this trial, the median overall survival (OS) was not reached with the combination regimen. Secondary end points of progression-free survival and overall response rate were improved with the doublet vs the TKI sorafenib (Nexavar). Moreover, the combination was found to be well tolerated, with minimal grade 3 or 4 adverse effects (AEs) reported, according to Ahn. Despite concern regarding the risk of bleeding, this AE was found to be nominal when patients were properly prescreened and managed, Ahn notes. Overall, the regimen is recommended for most patients with treatment-naïve HCC, Ahn says.

Patients in this population may also receive the STRIDE regimen comprised of the PD-L1 inhibitor durvalumab and the anti–CTLA-4 inhibitor tremelimumab based on results from the phase 3 HIMALAYA trial (NCT03298451) done in patients with unresectable HCC, Ahn adds. Data demonstrated an improvement in OS with durvalumab plus tremelimumab vs sorafenib, and ultimately led to the FDA approval of this regimen on October 21, 2022. Notably, the study did not require patients to undergo an esophagogastroduodenoscopy, Ahn adds. Therefore, patients with a known history of severe esophageal varices and/or risk of bleeding could benefit from this treatment alternative, he explains. However, the toxicity profile of this regimen is higher than other treatment options in this space, Ahn notes.

Although both ICI-based regimens may be effective for eligible patients, those with contraindications for immunotherapies may instead receive standard TKIs like sorafenib or lenvatinib (Lenvima), Ahn concludes.