Hope Persists as Treatment Landscape for HCC Expands Dramatically

Wasif M. Saif, MD

Wasif M. Saif, MD

Patients with hepatocellular carcinoma (HCC) have 6 FDA approved treatment options for the second-line setting, including 4 targeted therapies and 2 immunotherapies. This is a hopeful time for this heterogeneous disease as more research on new drugs and potential biomarkers continues, Wasif M. Saif, MD, said.

“The key element is hope,” Saif toldTargeted Oncology. “Our patients are diagnosed with cancer, and specifically, they are diagnosed with a deadly disease like HCC, which takes away hope. We need to bring them hope that not only are we going to take it off them, but we will also take out their cancer.”

Many abstracts at medical meetings during 2019 highlighted additional treatment options that are underway in this space, such as the phase III CheckMate 459 trial. Thisstudy demonstrated an improvement in overall survival (OS) with nivolumab (Opdivo)compared with sorafenib (Nexavar), the standard of care, in patients with unresectable HCC. The phase III IMbrave150 trial also demonstrated a statistically and clinically improved progression-free survival and OSwith the combination of atezolizumab (Tecentriq) plus bevacizumab (Avastin) compared with sorafenib in patients with HCC.

In July of 2019, the FDA also granted abreakthrough therapy designation to the combination of pembrolizumab (Keytruda) plus lenvatinib (Lenvima)for the treatment of patients with newly diagnosed, advanced, unresectable HCC that is not amenable to locoregional treatment. Lenvatinib is a tyrosine kinase inhibitor (TKI), like regorafenib (Stivarga), another agent approved by the FDA for the treatment of patients with HCC, and sorafenib. In combination with the immune checkpoint inhibitor pembrolizumab, the treatment regimen has demonstrated promise in previous data, according to Saif.

In an interview withTargeted Oncology, Saif, deputy physician in chief at Northwell Health Cancer Institute and a professor at the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, discussed the current treatment landscape and recent expansions in HCC that are providing him with hope for the field.

TARGETED ONCOLOGY: Could you share your thoughts on the treatment landscape of HCC beyond sorafenib?

Saif:HCC has been a very heterogeneous disease to treat, but we are very lucky to say we now have multiple agents available to treat patients who have failed the first-line therapy. If you look at the whole menu, we have 4 targeted agents and 2 immunotherapies available. However, we do not have any randomized data to help us decide which is the right patient for the right agent. I still believe we are not at precision oncology, but we can tailor therapy based on patient characteristics, the previous response, targets of the therapy, and the disease characteristics. There is no question now that we can now treat patients for second-line therapy.

In my practice and at other major institutions, we believe that more than 50% of the patients are now able to receive a second-line therapy. Immunotherapy has to be changed a lot because we have seen persistent responses in these patients. It is very hard to see a response in patients of HCC.

TARGETED ONCOLOGY: Were there any data at ESMO in the field of HCC you found particularly interesting?

Saif:There was a very important phase III study presented. This was looking at nivolumab, an anti—PD-L1 drug or immunotherapy, compared against sorafenib in the frontline setting. Although the study did not meet its primary end point, the study showed this drug is clinically beneficial to the patient. The side effects, discontinuation due to side effects, and the quality of life all favored nivolumab, which further validated the data. Initially keeping the nivolumab was approved by the FDA based on single-arm phase II data.

TARGETED ONCOLOGY: What were your thoughts on the IMbrave150 trial?

Saif:This is an interesting study because now we are trying to go beyond those 2 different targeted agents being combined together. We all say cancer is a very promiscuous disease, and sometimes targeting with 1 agent may not be helpful. We already know there are different ways to develop resistance to anti-VGEF therapy.By combining the drugs in this study, this is the way to see we can overcome the resistance and provide a meaningful benefit to patients with HCC.

TARGETED ONCOLOGY: Could you discuss the combination of lenvatinib plus pembrolizumab, which was granted a breakthrough therapy designation by the FDA?

Saif:First of all, these are 2 different drugs. Lenvatinib is basically another TKI, although it has some potential benefit of getting more targets compared to regorafenib and sorafenib. On the other hand, pembrolizumab is basically immunotherapy. By combining them together and as long as we can keep the toxicity in control, I am hoping combining these agents will lead to much better results because the first studies have shown persistently a better response rate than immunotherapy.

I’m definitely hopeful because it is a time to be hopeful. A few years ago, we had nothing to treat patients with HCC. Now we have 6 agents competing with each other in the second-line setting. Knowing these agents work differently and have different side effect profiles, I am very hopeful that the signs and efforts will lead to a fruitful outcome for these patients.

TARGETED ONCOLOGY: What are your key takeaways on today’s treatment landscape for HCC?

Saif:The key element is hope. The first thing we need to do is carry on hope. I think this comes from the effort we are putting out. Hope also comes from educating people because it is very important. Our patients are diagnosed with cancer, and specifically, they are diagnosed with a deadly disease like HCC, which takes away hope. We need to bring them hope that not only are we going to take it off them, but we will also take out their cancer. We are making efforts to improve outcomes for these patients by developing new drugs.