Investigating Treatment Options for HCC at Memorial Sloan Kettering

Ghassan Abou-Alfa, MD

Ghassan Abou-Alfa, MD

At Memorial Sloan Kettering Cancer Center, Ghassan Abou-Alfa, MD, and colleagues are investigating a number of treatment options for patients with hepatocellular carcinoma (HCC). With 5 tyrosine kinase inhibitors (TKIs) and a checkpoint inhibitor of which 3 are FDA approved and 1 received conditional approval, there are a number of discoveries still to be made.

There are a several clinical trials currently taking place at Memorial Sloan Kettering, including the combination study of durvalumab (Imfinzi) plus tremelimumab. Abou-Alfa also mentioned trials looking at combinations of bevacizumab (Avastin) plus atezolizumab, and lenvatinib (Lenvima) plus pembrolizumab (Keytruda).

In an interview withTargeted Oncology, Abou-Alfa discussed those clinical trials and other investigated treatment options for patients with HCC. He also highlighted his hopes for the future of this disease.

TARGETED ONCOLOGY: You’re involved in a number of trials at Memorial Sloan Kettering. Can you give us an overview of some of the research you’re currently working on?

Abou-Alfa:There is quite a bit going on, and not only talking about the clinical trials at Memorial Sloan Kettering, but talking about the whole field of HCC. There is excitement about the approval of recent drugs. These include lenvatinib, regorafenib, and the conditional approval of nivolumab. The positive results of cabozantinib and ramucirumab are worth noting. All suchdrugs are bringing a lot of wealth in regard to the choices of therapy for liver cancer. We now have literally 5 TKIs and 1 checkpoint inhibitor available after more than10 years with only 1 drug.

The trials at the moment are focusing on few efforts. Such efforts include the evaluation of the combination of TKIs and checkpoint inhibitors, and the combination of checkpoint inhibitors.

One important trial is the HIMALAYA study that is looking at two checkpoint inhibitors, durvalumab and tremelimumab, an anti-PD-1 and an anti-CTLA-4 combination.

The combination of checkpoint inhibitor plus the TKIs is intriguing. We are waiting for the follow-up to the bevacizumab plus atezolizumab study that was reported in a poster at ASCO with a suggested high response rate despite the reference population was not an intent to treat one. We look forward to hear more explanations. There is now a phase III trial that is evaluating this combination. There are other options that look intriguing along the same line among which the lenvatinib plus pembrolizumab combination.

The second important component to these trials is the combination of local therapy plus systemic therapy. Despite the prior efforts in regard to sorafenib plus embolization that did not work, at the moment there is quite a bit of interest in the use of embolizationplus a checkpoint inhibitor. At Memorial Sloan Kettering, we are conducting a clinical trial of nivolumab plus chemoembolization.

Thirdly, despite its novely, there is a lot of interest and momentum in the evaluation of CAR T. Lot of pre-clinical and early clinical efforts are underway.

TARGETED ONCOLOGY: What research are you particularly excited about in the field of HCC?

Abou-Alfa:Novel approaches like Pexa-Vec vaccinia intra-turmoral treatment and CAR T are both of interest. The basic science of the disease is very important to learn more about. We are currently leading a worldwide effort looking at the genetic makeup of tumors from different etiologies and ethnicities all over the world at the DNA, RNA and protein level.

TARGETED ONCOLOGY: What are some of the challenges you think still exist in HCC?

Abou-Alfa:The challenge remains that HCC is a difficult disease to take care of. Patinet with HCC have ingeneral two diseases in one, the cancer itself and the associated cirrhosis. Handling those pieces of the puzzle is key!

Also, we cannot forget about particular situations and particular patient groups. For example, HIV that happens at the same time as HCC. We have a very poor understanding of this. In my capacity as the head of the GI/Liver Non-AIDS-Defining Cancer NCI group, I am working on an effort of that nature.

TARGETED ONCOLOGY: What kind of advice would you give to a community oncologist faced with a patient with HCC?

Abou-Alfa: