Daneng Li, MD
The paradigms of hepatocellular carcinoma (HCC) and neuroendocrine tumors (NETs) have both had recent therapeutic additions; however, more research in each area continues to be conducted to further improve survival outcomes.
At the 2019 Gastrointestinal Cancers Symposium, one open-label, single-center, randomized, phase II trial evaluated the combination of nivolumab (Opdivo) and ipilimumab (Yervoy) compared with nivolumab alone in patients with resectable HCC. Preliminary results showed that out of 8 patients, 3 (37.5%) experienced a pathologic complete response (pCR) with the combination treatment; 2 were seen in the nivolumab monotherapy arm and 1 was observed in the combination arm.
This study is a move to an earlier setting for HCC and away from the metastatic HCC setting, explained Daneng Li, MD, where several clinical trials and recently FDA-approved therapies have been explored.
In the NET armamentarium, Li discussed how next steps for research should focus on the optimal sequence of therapies, as well as determining what potential role, if any, checkpoint inhibition has in these patients.
In an interview during the 2019 OncLive®
State of the Science SummitTM
on Gastrointestinal Cancers, Li, an assistant clinical professor, Department of Medical Oncology and Therapeutics Research, and a medical oncologist at City of Hope, shed light on some of the currently available regimens and ongoing research efforts being conducted in HCC and NETs.
OncLive: What studies in HCC were presented at the 2019 Gastrointestinal Cancers Symposium?
: There were various studies being presented in HCC. One thought-provoking study was a study coming out of The University of Texas MD Anderson Cancer Center, which is looking at preoperative immunotherapy with either nivolumab alone or the combination of nivolumab and ipilimumab. This is very interesting, because the overall landscape of HCC is rapidly changing.
Traditionally, in terms of current FDA-approved treatments, we have oral TKIs and now there are immunotherapies already FDA approved in the second-line setting with single-agent nivolumab as well as pembrolizumab (Keytruda). However, a lot of the focus on HCC has been in the frontline metastatic setting, whether it is combination immunotherapy or immunotherapy with targeted agents. Many are undergoing phase III testing already.
The study that was presented moved the bar even further [from] the first-line metastatic setting, and it looked at the preoperative or adjuvant setting for resectable HCC. This was a preliminary analysis coming out of The University of Texas MD Anderson Cancer Center, where patients were treated with immunotherapy perioperatively; [the investigators] were really looking for pCRs.
As a preliminary interim analysis, out of 8 patients, what they saw was that 3 patients had a pCR, which was fairly remarkable in this population and [patients] were able to undergo successful surgery. This is really moving the bar upfront for patients with early-stage HCC, to see whether or not immunotherapy has a preoperative or adjuvant role.
Ultimately, the more thought-provoking question in the long-term is, “Can patients who potentially have borderline resectable disease be downstaged with frontline immuno-oncology treatments to get them to resectability?” [Another challenge is can we] ultimately select for the true patients who will benefit from this in the long-term in terms of decreasing the risk of recurrence.
Cabozantinib (Cabometyx) has been approved in the second-line setting. How is this drug impacting the landscape?
Cabozantinib has an interesting role in the overall landscape for HCC. Currently in the second-line setting for HCC, it is somewhat of a crowded space. You have regorafenib (Stivarga), which is really for patients who can tolerate sorafenib (Nexavar) in the first-line setting, and then you have the recent approvals of cabozantinib, as well as prior approvals of nivolumab and pembrolizumab.