NCCN Guidelines for Hepatocellular Carcinoma 1.
2023 – Interim on 2/17/23
Guideline Page
and Request
HCC-G (1 of 2)
External Request
Submission from Genentech (04/06/2022) to consider
expanding the use of atezolizumab + bevacizumab as
a first-line treatment option for metastatic HCC to
patients with Child-Pugh B cirrhosis based on a real-
world study that evaluated the safety and tolerability of
atezolizumab +bevacizumab in Child-Pugh A and
Child-Pugh B patients.
HCC-G (1 of 2)
External Request
Submission from Bristol Myers Squibb (04/11/2022) to
request the panel’s consideration of the enclosed data
and to include nivolumab in combination with
ipilimumab as a treatment option for patients with
tissue TMB-H (tTMB-H) hepatobiliary cancers who are
refractory to standard therapies or have no standard
treatment options available.
Institution Vote
Panel Discussion/References
YES NO ABSTAIN ABSENT
Based on a review of the data and discussion, the 19 3 2 9
panel consensus supported the inclusion of
atezolizumab + bevacizumab as a first-line systemic
therapy option for patients with advanced HCC
(unresectable disease and not a transplant
candidate; liver-confined disease, inoperable by
performance status, comorbidity, or with minimal or
uncertain extrahepatic disease; or metastatic disease
or extensive liver tumor burden) with Child-Pugh
Class B cirrhosis. This is a category 2A, useful in
certain circumstances recommendation.
See Submission for references.
Based on a review of the data and discussion, the
panel consensus supported the inclusion of
nivolumab in combination with ipilimumab as a
systemic therapy option for patients with advanced
HCC (unresectable disease and not a transplant
candidate; liver-confined disease, inoperable by
performance status, comorbidity, or with minimal or
uncertain extrahepatic disease; or metastatic disease
or extensive liver tumor burden) with TMB-H tumors.
First-line systemic therapy: This is a category 2B, 11 9 4 9
useful in certain circumstances recommendation.
Subsequent-line systemic therapy if disease 16 5 3 9
progression: This is a category 2B, useful in certain
circumstances recommendation.
Based on a review of the data and discussion, the 15 2 7 9
panel consensus supported the inclusion of the
following footnote in the subsequent-line setting: For
patients with disease refractory to standard therapies
or who have no standard treatment options available
See Submission for references.
NCCN Guidelines for Hepatocellular Carcinoma 1.2023 – Interim on 2/17/23
HCC-G (1 of 2)
Internal request: Consider clarifying whether nivolumab
in combination with ipilimumab is a subsequent-line
systemic therapy option if disease progression in
patients who have not been previously treated with a
checkpoint inhibitor:
Based on a review of the data, the panel 11 5 8 9
recommends nivolumab in combination with
ipilimumab as a subsequent-line systemic therapy
option if disease progression for patients with
advanced HCC who have not been previously treated
with atezolizumab + bevacizumab.
Based on a review of the data and discussion, the 10 6 8 9
panel recommends nivolumab in combination with
ipilimumab as a subsequent-line systemic therapy
option if disease progression for patients with
advanced HCC who have not been previously treated
with pembrolizumab, nivolumab, or durvalumab ±
tremelimumab-actl.
Based on the data, the following footnote was 15 6 3 9
included for nivolumab in combination with
ipilimumab as a subsequent-line systemic therapy
option if disease progression for patients with
advanced HCC (unresectable disease and not a
transplant candidate; liver-confined disease,
inoperable by performance status, comorbidity, or
with minimal or uncertain extrahepatic disease; or
metastatic disease or extensive liver tumor burden):
For patients who have not been previously treated
with a checkpoint inhibitor because
there is a lack of data for subsequent use of
immunotherapy in patients who have
previously been treated with a checkpoint inhibitor.