Tislelizumab Pushes HCC Field Forward With 2024 NCCN Guideline Category 1 Recommendation

Alan P. Venook, MD

Identifying a biomarker to predict which patients with hepatocellular carcinoma (HCC) are most likely to respond to checkpoint inhibitor therapy is a necessary next step in the field especially as the addition of tislelizumab-jsgr (Tevimbra) to the NCCN Clinical Practice Guidelines in Oncology for HCC as a category 1 other recommended regimen provided another checkpoint inhibitor option, according to Alan P. Venook, MD.

“[Within gastrointestinal cancers], the changes have mostly been in HCC, and the evolution of different combinations of biologics and immunotherapies have made their way to the top of the heap,” Venook, a member of the HCC NCCN guideline panel, said of the 2024 guideline changes in an interview with OncLive. “I can’t emphasize enough how these are living documents and how rapidly they can change. Our goal is to stay on top of it and stay ahead.”

The Most Notable 2024 NCCN Guideline Revisions in HCC¹:

• For first-line systemic therapy:
  • Tislelizumab was added under other recommended regimens (category 1)
  • Repotrectinib (Augtyro) was added under useful in certain circumstances (category 2B) for NTRK gene-fusion positive tumors
  • Nivolumab (Opdivo), atezolizumab (Tecentriq) plus bevacizumab (Avastin), and nivolumab plus ipilimumab (Yervoy; for tumor mutational burden high tumors) were removed from useful in certain circumstances regimens
• For subsequent-line systemic therapy if disease progression occurred:
  • Nivolumab plus ipilimumab (for tumor mutational burden-high tumors) was removed from useful in certain circumstances regimens
• Treatment top pathways were revised to:
  • Resection (preferred)
  • Transplant (preferred if transplant criteria are met)
    • Refer to liver transplant center and bridge therapy as indicated
  • Locoregional therapy
    • Ablation (preferred)
• The following new sections were added: Principles of Mixed HCC-CCA, Principles of Pathology, and Principles of Liver Functional Assessment

In an interview with OncLive, Venook highlighted notable NCCN guideline updates in HCC from 2024 as well as next steps in the field, and considerations when implementing the changes into practice. He is the Madden Family Distinguished Professorship in Medical Oncology and Translational Research at UCSF, the Shorenstein Associate Director for Program Development at the Helen Diller Family Comprehensive Cancer Center, and a professor in the Department of Medicine at UCSF in San Francisco, California.

“HCC is evolving so rapidly,” he said. Another update to the guidelines will be made public in 2025, but the latest version added tislelizumab as a category 1 recommendation along with other regimens as a first-line systemic therapy. The update was made based on a study that compared tislelizumab with sorafenib with tislelizumab having an advantage in objective response rate.

However, it’s unclear if the many agents approved to treat HCC are different from one another or making advances against the disease.

“Distinguishing one from the other is impossible and it is likely that these [agents] will never be compared head-to-head because they are [manufactured by] different companies that have the indication from different study designs and it’s not clear that they want to put their drugs up against each other,” Venook said.

The flaw with current HCC studies is that they usually evaluate median survival outcomes, and “it’s not clear that these treatments make a difference because many patients get no benefit at all.” There are a subset of patients who do benefit, and the end points have to assess the patients who don’t progress at a certain period of time.

He reminded community oncologists that it’s key to keep downloading the latest versions of the guidelines, because they are living documents that get updated regularly.

Read the full interview at OncLive.

Reference

1. NCCN. Clinical Practice Guidelines in Oncology. Hepatocellular carcinoma, version 3.2024. Accessed November 18, 2024. https://www.nccn.org/professionals/physician_gls/pdf/hcc.pdf