He said the trial in HCC is open and actively accruing patients who are slated for surgery (ClinicalTrials.gov Identifier: NCT03916627). The researchers have started a neoadjuvant trial of immunotherapy using PD-1 blockade, and once that has accrued, they will also be investigating combination approaches of a PD-1–blocking antibodies with myeloid-modifying agents in patients with HCC.

Benjamin Tan, MD, who is associate professor of medicine at Washington University School of Medicine and a medical oncologist at Siteman Cancer Center in St. Louis, Missouri, said PD-1 inhibitors are increasingly being combined with other systemic therapies and locoregional treatments. “These agents are also being investigated after ablation or resection. A clinical dilemma for treatment with immunotherapy in potentially curable patients may occur in those who could be eligible for transplantation. Recent results2 showed that the combination of a PD-blockage agent plus an angiogenesis inhibitor achieved significant benefit for advanced HCC patients,” Dr Tan told Cancer Therapy Advisor.

He said currently it’s unclear if cemiplimab is different than other PD antagonists, but single-agent use in phase 3 had negative results in the treatment of advanced HCC.3,4 In just the past 2 years, 4 new PD-1 monoclonal antibodies were approved globally, according to researchers from The Cancer Research Institute (CRI).5 It conducted a survey and found interest in immunotherapy has skyrocketed in the last 24 months. There are now 2975 active trials evaluating PD-1/PD-L1 immuno-oncology therapies, representing a 97.5% increase since 2017, according to the organization.6

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Liver specialist Stacey Stein, MD, who is with Yale Cancer Center and Smilow Cancer Hospital, New Haven, Connecticut, said combination therapies are showing promise, and she believes the treatment landscape for HCC is about to change significantly. “I think we are going to see a transformation in the field,” Dr Stein said in an interview with Cancer Therapy Advisor. “Things are going to change and we are going to see more synergy with these combinations.”

Dr Tan agreed, and said the identification of patients with HCC who respond — and do so in a durable fashion to checkpoint blockade — would help clarify the subset of patients with HCC who may benefit from these agents. “The optimal sequence of treatment with other agents or procedures will also need to be clarified. I think single-agent PD inhibition will not advance the field. Possibly targeting other pathways with immunotherapy appears more attractive than single-agent treatment,” said Dr Tan.

Dr Stein noted that introducing immunotherapy before surgery is being investigated, but there are still many unanswered questions about this approach in patients with HCC. “Toxicities with the combinations approach will have to be weighed against the incremental benefits of the combination,” said Dr Stein. “It is very promising because for years we have not seen much new for HCC and now there is much more interest.”

Disclosures: Dr Marron disclosed he was on an advisory board for Regeneron in 2019. Dr Tan has no related disclosures to report. Dr Stein has no related disclosures to report.

References

  1. Icahn School of Medicine at Mount Sinai. Human immune monitoring center at Mount Sinai to analyze the effectiveness of a novel cancer therapy drug [press release]. Published November 5, 2019. Accessed January 9, 2020.
  2. A-L Cheng, S Qin, M Ikeda, et al. LBA3 IMbrave150: Efficacy and safety results from a ph III study evaluating atezolizumab (atezo) + bevacizumab (bev) vs sorafenib (sor) as first treatment (tx) for patients (pts) with unresectable hepatocellular carcinoma (HCC). Ann Oncol. 2019;30(suppl_9):mdz446.002.
  3. Yau T, Park JW, Finn RS, et al. LBA38_PR CheckMate 459: A randomized, multi-center phase III study of nivolumab (NIVO) vs sorafenib (SOR) as first-line (1L) treatment in patients (pts) with advanced hepatocellular carcinoma (aHCC). Ann Oncol. 2019;30(suppl_5): v851-v934.
  4. Finn RS, Ryoo B-Y, Merle P. Results of KEYNOTE-240: phase 3 study of pembrolizumab (Pembro) vs best supportive care (BSC) for second line therapy in advanced hepatocellular carcinoma (HCC). J Clin Oncol. 2019;37(15_suppl):4004-4004.
  5. Yu JX, Hodge JP, Oliva C, Neftelinov ST, Hubbard-Lucey VM, Tang, J. Trends in clinical development of PD-1/PD-L1 inhibitors [published online November 4, 2019]. Nat Rev. Drug. Discov. doi: 10.1038/d41573-019-00182-w
  6. The Cancer Research Institute. Updated report on trends in global PD-1/PD-L1 immunotherapy clinical development from the Cancer Research Institute Published in Nature Reviews Drug Discovery [press release]. Published November 4, 2019. Accessed January 9, 2020.