Ghassan Abou-Alfa, MD

Ghassan K. Abou-Alfa, MD, a medical oncologist at Memorial Sloan Kettering Cancer Center, discusses the phase 2 study of tislelizumab in patients with unresectable hepatocellular carcinoma (HCC).

The study was conducted in the subgroup of patients with Child-Pugh A and Barcelona Clinical Liver Cancer stage B/C who were previously treated with at least 1 prior systemic therapy.

Tislelizumab achieved durable response in the study and was well-tolerate by patients. According to Abou-Alfa, the data were very encouraging and signal hope for the success of a phase 3 study of tislelizumab, which is ongoing. 

 In brief, we're quite excited that tislelizumab as another anti-PD-1, but with a very important specificity and regard to its mechanisms of action have been evaluated in this phase 2 study and led to the finding of important results, among which is an increase response rate of close to about 13% with importantly, 2 complete responses and 29 partial responses. And if anything, this translated into improvement in outcome, over a medium follow up close to about 9 to 10 months. Median overall survival was 12.4 months and medium progression- free survival was 2.7 months.

It is important to note the 1-year overall survival was close to 52%. No doubt that this is very encouraging, especially that the therapy was tolerable. And of course, we look forward for the results of the ongoing randomized phase 3 trial evaluating tislelizumab compared to the standard, sorafenib, as first line therapy for patients with advanced unresectable HCC

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Ghassan K. Abou-Alfa, MD,discusses the phase 2 study of tislelizumab in patients with unresectable hepatocellular carcinoma.

Exploring Tislelizumab for Unresectable HCC

Ghasson K. Abou-Alfa, MD, a medical oncologist at Memorial Sloan Kettering Cancer Center, discusses that phase 2 study of tislelizumab (BGB-A317) as treatment of patients with unresectable hepatocellular carcinoma (HCC).

The study assessed the primary end point of objective response rate in 249 patients with HCC. The treatment induced durable responses in these patients and was well-tolerated. Further exploration of the treatment strategy is underway in a phase 3 randomized study of tislelizumab versus the current standard of care therapy, sorafenib (Nexavar).

 In brief, we're quite excited that tislelizumab is another anti PD-1, but with a very important specificity in regard to it mechanism of action have been evaluated in this phase 2 study and lead to the finding of important results, among which an increase response rate of close to about 30%, and importantly, 2 complete responses and 29 partial responses. If anything, this translated into improvement in outcome over a medium follow- up close to 9 to 10 months. Median overall survival was 12.4 months and medium progression free survival was 2.7 months with importance to re-note that the 1-year overall survival was close to 52%. Know that this is very encouraging, especially that the therapy was tolerable. And of course, we look forward for the results of the ongoing growth of a specific drug evaluating business compared to the standard, so after first-line therapy for patient with advanced, unresectable HCC.

 Tislelizumab has certain particularities, and it really does. If anything, yes, it's an anti PD-1, but intriguingly, it has a very high affinity and specificity to PD-1, which is engineered because of the minimization of the binding of the FC gamma receptor on macrophages to limit the antibody dependent phagocytosis. So, as we all know, the PD-1 is sitting like a chair, where the T cells will come in and they are invited to sit on and that's why they don't attack the cell membrane of the cancer cell. And oral anti PD-1 does escape this chair also the new cell can fall into play. Interestingly, however, with the FC gamma, this might become a little bit a more laborious process. And if anything, the tie in of the binding of the FC gamma to the macrophages, which means the T cells are bound to the macrophage will prevent that interaction from happening as powerful as can be. With this extra acid that tislelizumab provides by minimizing the binding of the FC gamma receptor to the macrophages , it rather kind of invites the direct attack of the T cells onto the tumor.

Ghasson K. Abou-Alfa, MD, discusses that phase 2 study of tislelizumab  as treatment of patients with unresectable hepatocellular carcinoma.

Utilizing Tislelizumab to Treat Unresectable Hepatocellular Carcinoma

Ghassan Abou-Alfa, MD, a medical oncologist at Memorial Sloan Kettering Cancer Center, discusses the approved agents available for the treatment of hepatocellular carcinoma (HCC). Compared to 2007 when there was only 1 agent available, sorafenib (Nexavar), there is now a great number of options for these patients.

In the frontline setting, lenvatinib (Lenvima) is approved. In the second-line, regorafenib (Stivarga) is approved for use after patients have progressed on sorafenib. There is also a conditional approval for nivolumab (Opdivo) in the second-line setting of HCC.

Encouraging data is available for cabozantinib (Cabometyx) in the second- and third-line settings, as well as ramucirumab (Cyramza) in the second-line for patients with high alpha-fetoprotein.

Ghassan Abou-Alfa, MD, discusses the approved agents available for the treatment of hepatocellular carcinoma. Compared to 2007 when there was only 1 agent available, sorafenib, there is now a great number of options for these patients.

Current Agents Approved for Treatment of HCC

Ghassan Abou-Alfa, MD, medical oncologist, Memorial Sloan Kettering, discusses the important role that locoregional therapy plays in the treatment of liver cancer.

The Role of Locoregional Therapy in the Treatment of Liver Cancer

Ghassan Abou-Alfa, MD, medical oncologist, Memorial Sloan Kettering Cancer Center, talks about first- and second-line treatments for hepatocellular carcinoma (HCC). He says sorafenib is currently the&nbsp;only first-line treatment approved for HCC based on the&nbsp;SHARP trial, where the treatment showed improved survival in patients from 7.9 months to 10.7 months.

Abou-Alfa says he finds it interesting that second-line therapies are already being investigated despite there not being many options for first-line treatments. He says nivolumab and pembrolizumab may have a place in the treatment of HCC.

Ghassan Abou-Alfa says serafnib is currently the only first-line treatment approved for HCC based on the SHARP trial, where the treatment showed improved survival in patients from 7.9 months to 10.7 months.

Ghassan Abou-Alfa, MD | Authors

Articles

Exploring Tislelizumab for Unresectable HCC

Utilizing Tislelizumab to Treat Unresectable Hepatocellular Carcinoma

Current Agents Approved for Treatment of HCC

The Role of Locoregional Therapy in the Treatment of Liver Cancer

Dr. Ghassan Abou-Alfa on Possible Second-Line Treatments for HCC Patients