A Pilot Study of Pembrolizumab in Combination With Y90 Radioembolization in Subjects With Poor Prognosis Hepatocellular Carcinoma

Videos

William Harris, MD, presents the study design and rationale for HCRN GI15-225, an open-label, single-arm multicenter, pilot study exploring whether using immunotherapy drugs in combination with locoregional therapies for patients with non-metastatic HCC is safe and beneficial, using pembrolizumab every 3 weeks starting 1 week before initial Y90 radioembolization.

William P. Harris, MD, physician, Seattle Cancer Care Alliance, associate professor, Division of Oncology, University of Washington (UW) School of Medicine, physician, UW Medicine, associate professor, Clinical Research Division, Fred Hutchinson Cancer Research Center, discusses remaining questions regarding treatment sequencing after atezolizumab (Tecentriq) and bevacizumab (Avastin) in hepatocellular carcinoma (HCC). 

Although the integration of first-line atezolizumab plus bevacizumab has been revolutionary to the treatment of most patients with HCC, questions regarding sequencing after the doublet remain unanswered, Harris says. As such, more clinical trials are needed to identify and optimize available second- and third-line options for patients.

Additionally, trials are needed to determine whether there is a role for PD-1/PD-L1 inhibition among patients who progress on checkpoint inhibitors, as well as to evaluate experimental novel agents and adoptive T-cell therapies, Harris says. Finally, data are needed to determine if and where localized therapy fits into the treatment plan for patients who progress on checkpoint inhibitors, Harris concludes.

William P. Harris, MD, discusses remaining questions regarding treatment sequencing after atezolizumab and bevacizumab in hepatocellular carcinoma.



Dr. Harris on Remaining Questions With Treatment Sequencing in HCC 

William P. Harris, MD, physician, Seattle Cancer Care Alliance, associate professor, Division of Oncology, University of Washington (UW) School of Medicine, physician, UW Medicine, associate professor, Clinical Research Division, Fred Hutchinson Cancer Research Center, discusses updated data from the phase 3 IMbrave150 study (NCT03434379) in hepatocellular carcinoma (HCC).

The IMbrave150 study, which evaluated frontline atezolizumab (Tecentriq) plus bevacizumab (Avastin) vs sorafenib (Nexavar) in patients with unresectable HCC, was pivotal because it was the first to show superiority of a regimen compared with sorafenib in this patient population, according to Harris. Data from the trial show response rates of approximately 30%, as well as a median overall survival of at least 19 months or more, Harris explains. Moreover, in a subset of patients showed prolonged, durable responses.

Additionally, the toxicity profile of the combination is manageable, given that appropriate patients are chosen for treatment, Harries notes. The trial examined patients with Child-Pugh class A, and it remains to be seen whether similar safety and efficacy will also be seen in Child-Pugh class B, Harris continues. Patients under consideration for this treatment regimen should undergo upper endoscopy with the appropriate management before initiation, and those with high risk of bleeding should be excluded, Harris concludes.

William P. Harris, MD, discusses updated data from the phase 3 IMbrave150 study in hepatocellular carcinoma.

Dr. Harris on IMbrave150 Results With Atezolizumab/Bevacizumab in HCC

William P. Harris, MD, physician, Seattle Cancer Care Alliance, associate professor, Division of Oncology, University of Washington (UW) School of Medicine, physician, UW Medicine, associate professor, Clinical Research Division, Fred Hutchinson Cancer Research Center, discusses the adoption of immunotherapy in advanced hepatocellular carcinoma (HCC).

In recent years, the integration of immunotherapy into the treatment landscape of advanced HCC has been a significant advance in the treatment of this patient population, Harris says. Moreover, the data from the phase 3 IMbrave150 trial (NCT03434379) solidified the role for immunotherapy as a standard frontline treatment option for this patient population. Based on findings from the IMbrave150 study, in May 2020, the FDA approved the combination of atezolizumab (Tecentriq) and bevacizumab (Avastin) for the treatment of patients with unresectable or metastatic HCC who have not received prior systemic therapy. 

Additionally, several studies evaluating immunotherapy are ongoing in advanced HCC, Harris adds.

Ultimately, immunotherapy has dramatically transformed the way patients with HCC are treated, Harris says. The treatment provides the opportunity for patients to derive a prolonged response and without significant toxicity that could compromise quality of life, Harris concludes.

William P. Harris, MD, discusses the adoption of immunotherapy in advanced hepatocellular carcinoma. 



William P. Harris, MD

Articles

A Pilot Study of Pembrolizumab in Combination With Y90 Radioembolization in Subjects With Poor Prognosis Hepatocellular Carcinoma

Dr. Harris on Remaining Questions With Treatment Sequencing in HCC

Dr. Harris on IMbrave150 Results With Atezolizumab/Bevacizumab in HCC

Dr. Harris on the Adoption of Immunotherapy in Advanced HCC