Dr. Kundranda on the Sequencing of Second-Line Therapies in HCC

Madappa Kundranda, MD, PhD, director, Gastrointestinal Oncology Program, deputy chief, Division of Medical Oncology, Banner MD Anderson Cancer Center, discusses the sequencing of second-line therapies in hepatocellular carcinoma (HCC).

Treatment selection in the second-line setting should be primarily based on a patient's eligibility for immuno-oncology (IO) therapy in the first line, Kundranda begins. Those who are eligible for frontline IO therapy may receive atezolizumab (Tecentriq) and bevicizumab (Avastin), Kundranda says. In accordance with results from the phase 3 HIMALAYA trial (NCT03298451) in unresectable HCC, these patients may also receive the STRIDE regimen of durvalumab (Imfinzi) and tremelimumab (Imjudo) in the frontline setting, he states. 

Patients who have prior exposure to these regimens could then receive a TKI such as sorafenib (Nexavar), lenvatinib (Lenvima), cabozantinib (Cabometyx), or regorafenib (Stivarga), Kundranda recommends.

Patients who are ineligible for immune checkpoint inhibitors (ICIs) and were previously treated with frontline sorafenib or lenvatinib can be re-evaluated for ICI exclusion factors in the second line, Kundranda says. If this factor is no longer present, patients could be eligible for treatment with ICIs, he explains. Patients with HCC who display alpha-fetoprotein (AFP) levels above 400 may also be candidates for ramucirumab (Cyramza) based on data from the phase 3 REACH-2 trial (NCT02435433), Kundranda says. Notably, the patient population in REACH-2 had received sorafenib as frontline therapy, Kundranda notes.

Pembrolizumab (Keytruda) may be an optimal IO therapy for patients who are ineligible for TKIs or anti-angiogenic therapies, Kundranda says. Additionally, patients with HCC who show B7-H3 overexpression may receive single-agent pembrolizumab, provided they have previously received sorafenib, Kundranda details. Patients with B7-H3 are often seen in clinical practice, as this immunoregulatory protein is commonly expressed in HCC. Notably, in July 2021, nivolumab (Opdivo) was withdrawn from the United States market as a single agent for patients with HCC who received prior sorafenib.

Editor's Note: Dr. Kundranda reports serving as a consultant for Bayer, Bristol-Meyers Squibb, AstraZeneca, Oncocyte, Steris; he reports receiving research funding from Bristol-Meyers Squibb, Bayer and Oncocyte.