Ahmed O. Kaseb, MD, a professor in the Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, at The University of Texas MD Anderson Cancer Center, discusses the safety profile of the combination of atezolizumab (Tecentriq) and bevacizumab (Avastin) in hepatocellular carcinoma (HCC).

The phase 3 IMbrave150 trial enrolled patients with unresectable HCC and randomized them to receive treatment with atezolizumab in combination with bevacizumab or sorafenib. The adverse events (AEs) reported in both arms of the trial were expected, says Kaseb. More gastrointestinal and skin manifestations were observed in the sorafenib arm, whereas more bleeding episodes, hypertensive episodes, and proteinuria were reported in the combination arm. Grade 3 to 4 AEs occurred in 57% of patients in the combination arm versus 55% of patients in the sorafenib arm. Grade 5 AEs occurred in 5% and 6% of patients, respectively. The risk-benefit ratio must be weighed for the combination. Comorbidities and the current tumor burden must also be considered to determine which regimen to start with, concludes Kaseb.

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Ahmed O. Kaseb, MD, discusses the safety profile of the combination of atezolizumab and bevacizumab in hepatocellular carcinoma.

Dr. Kaseb on Safety Profile of Atezolizumab Plus Bevacizumab in HCC

Ahmed O. Kaseb, MD, a professor in the Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, at The University of Texas MD Anderson Cancer Center, discusses research with targeted therapy in hepatocellular carcinoma (HCC).

FGF inhibitors and TGF-β inhibitors are being evaluated, says Kaseb. Notably, tumors with advanced cirrhosis tend to have molecular alterations in TGF-β. Additionally, some studies have looked at 

 alterations. However, the overall percentage of patients with potentially targetable alterations is less than 5%, says Kaseb. One Asian study evaluated the use of RAS inhibitors in only 1% of the 2000 patients screened. TKIs, however, could have greater utility because they cause a downstream effect that could augment the effect of immunotherapy.

If TGF-β or STAT3 inhibitors, which are associated with immune suppression, can also be combined with immunotherapy, it could lead to greater utility in the field, explains Kaseb. At The University of Texas MD Anderson Cancer Center, investigators are planning a study that will evaluate STAT3 inhibitors plus checkpoint inhibitors, which could also help overcome acquired resistance mechanisms to immunotherapy, concludes Kaseb.

Dr. Kaseb on Research With Targeted Therapy in HCC

Ahmed O. Kaseb, MD, a professor in the Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, at The University of Texas MD Anderson Cancer Center, discusses the progression of therapeutic options for patients with hepatocellular carcinoma (HCC).

Sorafenib (Nexavar) and lenvatinib (Lenvima) will still have a role in the treatment of patients with HCC despite the approval of atezolizumab (Tecentriq) plus bevacizumab (Avastin). Results from a meta-analysis that was published in the 

 in 2017 examined all phase III studies with sorafenib and showed a trend toward improved survival and outcomes in patients with hepatitis C—related HCC. If a patient with a history of hepatitis C receives frontline atezolizumab plus bevacizumab and progresses, they can then receive sorafenib because of its potential increased efficacy in those with hepatitis C, explains Kaseb.

If a patient has a history of hepatitis B, then lenvatinib, cabozantinib (Cabometyx), or another second-line agent may be effective, as lenvatinib has been shown to have benefit in those with hepatitis B, explains Kaseb. Choosing the appropriate drug to start with will depend largely on the patient’s risk factors, adds Kaseb.

Down the line, more studies will be launched, and more approved doublets will emerge in HCC, predicts Kaseb. For example, one study is evaluating the use of pembrolizumab (Keytruda) plus lenvatinib. Another study is evaluating atezolizumab plus cabozantinib; yet another is examining durvalumab (Imfinzi) and tremelimumab. Many ongoing studies are expected to read out by the end of next year, and those data will hopefully lead to more available options for patients with HCC, concludes Kaseb.

Ahmed O. Kaseb, MD, discusses the progression of therapy options for patients with hepatocellular carcinoma.

Ahmed O. Kaseb, MD

Articles

Dr. Kaseb on Safety Profile of Atezolizumab Plus Bevacizumab in HCC

Dr. Kaseb on Research With Targeted Therapy in HCC

Dr. Kaseb on the Progression of HCC Research