Richard D. Kim, MD, Discusses the Evolving Role of Combination Therapies in HCC

CancerNetwork® sat down with Richard D. Kim, MD, of the Moffitt Cancer Center at the 2021 ASCO Annual Meeting to talk about the many ways oncologists can approach treating hepatocellular carcinoma with combination regimens.

At the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, CancerNetwork® spoke with Richard D. Kim, MD, of the Moffitt Cancer Center to discuss the role of combination therapies in the treatment of hepatocellular carcinoma (HCC). In particular, the investigators behind a phase 1b study (NCT03347292) sought to answer the question as to how patients with advanced HCC might respond to a combination of pembrolizumab (Keytruda) and regorafenib (Stivarga). The study found that there was good anti-tumor activity with a disease control rate of 91% with an 80 mg dose of regorafenib in combination with pembrolizumab.


In the past, we only had sorafenib [Nexavar] available for patients with advanced liver cancer. It really had a modest efficacy. Therefore, at that time, local therapy played a big role in [the treatment of many] patients. But now with these combinations evolving, such as atezolizumab [Tecentriq] plus bevacizumab [Avastin], or trosine kinase inhibitors [TKI] plus immunotherapy, if you look at the median survival of these patients, it is really hovering around 20 months [or more].

Therefore, since now we have a lot of drugs that we could use in this setting, this kind of combination will be moved [to earlier in treatment], to what we call in Barcelona stage B patients. In the past, those patients would get local therapy multiple times until they [progressed], and then they get referred to medical oncologists. But I do believe that this combination, whether [it is] an anti-VEGF plus immunotherapy or a TKI plus immunotherapy, will move up earlier in line where now we could use [them in] Barcelona stage B patients. That is one of the key movements that will happen in the future. Once again, this is where [we] really do need a multi-modality approach and we talked to our interventional radiologists to tell them, ‘Hey, we do have good combinations out there. ‘

Therefore, early referral to medical oncology, is a must in the setting. Also moving forward, because there are so many drugs out there for HCC, we have to learn how to sequence them. Right now, currently we have a couple of TKIs available that [have been] approved such as cabozantinib [Cabometyx], lenvatinib [Lenvima], regorafenib, [and] sorafenib. Now, in the setting of immunotherapy, where we are now combining it with immunotherapy plus TKI or anti VEGF plus immunotherapy in this setting, we have to learn how to sequence all these available agents. That is [going to] be key in how we practice in future.


El-Khoueiry A, Kim R, Harris W, et al. Updated results of a phase 1b study of regorafenib (REG) 80mg/day or 12omg/day plus pembrolizumab (PEMBRO) for first-line treatment of advanced hepatocellular carcinoma (HCC). J Clin Oncol. 2021;39(suppl 15):4078. doi:10.1200/JCO.2021.39.15_suppl.4078