Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

eUpdate – Hepatocellular Carcinoma Treatment Recommendations

eUpdate – Hepatocellular Carcinoma Treatment Recommendations

Published: 14 January 2020. Authors: ESMO Guidelines Committee

Note: Other eUpdates may have been published for these guidelines. All currently valid eUpdates can be accessed from the page displaying the full guidelines on this topic

Clinical Practice Guidelines

This eUpdate refers to Hepatocellular carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Vogel A, Cervantes A, Chau I et al. Ann Oncol 2018; 29 (Suppl 4): iv238–iv255.

Section

Management of early and intermediate HCC, Selective internal radiotherapy

Text update

Thus, in exceptional circumstances, for patients with liver-confined disease and preserved liver function in whom neither TACE nor systemic therapy is possible, SIRT may be considered.

Is replaced with:

Thus, in exceptional circumstances, for patients with liver-confined disease and preserved liver function in whom neither TACE nor systemic therapy is possible, SIRT may be considered [III, C].

Section

Table 4. BCLC staging and treatment options according to level of evidence and approval status

Text update

Under ‘Alternative treatment’:

BCLC stage B

SIRT (after TACE failure/ refractoriness)

Is replaced with:

SIRT (liver-confined, good liver function, no systemic therapy feasible)

 

BCLC stage C

Nivolumab (second-line) [III, B]

Pembrolizumab (second-line) [III, B]

SIRT (liver confined, good liver function, no systemic therapy feasible) [III, C]

 

Is replaced with:

SIRT (liver-confined, good liver function, no systemic therapy feasible)

 

Under ‘Treatment (standard of care)’:

Sorafenib (first-line) [I, A]

Regorafenib (second-line) [I, A; MCBS 4]

Lenvatinib (first-line) [I, A; MCBS 4]

Cabozantinib (second-line) [I, A; MCBS 3]

 

Is replaced with:

Sorafenib (first-line) [I, A]

Regorafenib (second-line) [I, A; MCBS 4]

Lenvatinib (first-line) [I, A; MCBS 4]

Cabozantinib (second-line) [I, A; MCBS 3]

Ramucirumab (AFPhigh, second-line) [I, A; MCBS 1]

The heading ‘Alternative treatment; Not yet EMA-approved’ is removed.

Section

Management of advanced disease, Systemic therapies for advanced HCC, Targeted second-line therapies

Text update

Ramucirumab can be considered for patients in second-line treatment with baseline AFP 400 ng/mL, well-preserved liver function and ECOG PS 0–1 [I, A; MCBS 1]. It received EMA approval in August 2019.

Section

Immunotherapies

Text update

Immunotherapy with nivolumab and pembrolizumab can be considered in patients who are intolerant to, or have progressed under, approved tyrosine kinase inhibitors, pending EMA approval [III, B]. For a definitive recommendation, it is necessary to wait for the results of randomised trials.

Is replaced with:

Immunotherapy in the form of combination regimens (atezolizumab and bevacizumab, IMbrave 150) or monotherapy (nivolumab, CheckMate 459) has been evaluated in untreated patients with BCLC B or C hepatoma, while pembrolizumab has been studied in patients who are intolerant to or have progressed under approved tyrosine kinase inhibitors. The first-line phase III CheckMate 459 trial, comparing sorafenib with nivolumab as a first-line treatment option failed to meet the primary endpoint of overall survival (OS). In contrast, the combination of atezolizumab with bevacizumab met both primary endpoints of OS and progression-free survival (PFS) compared with sorafenib, as it was associated with hazard ratios of 0.59 and 0.58 respectively. The second-line phase III KEYNOTE-240 trial of pembrolizumab failed to meet its co-primary endpoints of OS and PFS, compared with placebo plus best supportive care. For a definitive recommendation, it is necessary to wait for the final results of the randomised trials with more mature follow-up.

Section

Table 6. Summary of Recommendations, Management of advanced disease

Text update

  • Ramucirumab can be considered for patients in second-line patients with baseline AFP ≥400 ng/mL, well-preserved liver function and ECOG PS 0–1, pending EMA approval [I, A].

Is replaced with:

  • Ramucirumab can be considered as second-line treatment for patients with baseline AFP ≥400 ng/mL, well-preserved liver function and ECOG PS 0–1, and is now EMA-approved [I, A; MCBS 1].

 

  • Immunotherapy with nivolumab and pembrolizumab can be considered in patients who are intolerant to, or have progressed under, approved tyrosine kinase inhibitors, pending EMA approval [III, B]. For a definitive recommendation, it is necessary to wait for the results of randomised trials.

Is replaced with:

  • Immunotherapy with the combination of atezolizumab+bevacizumab, nivolumab (first-line) and pembrolizumab (second-line) have been evaluated for patients with irresectable hepatoma. In view of the positive results of the atezolizumab+bevacizumab combination, the regimen may be considered until mature data and EMA assessment are available for a definite recommendation  [III, B].

Section

Table 7ESMO-MCBS table for new therapies/indications in Hepatocellular cancera

The ESMO-MCBS table is updated to include a new line for ramucirumab.

Therapy

Lenvatinib versus sorafenib in first-line treatment

Disease setting

First-line unresectable hepatocellular carcinoma

Trial

A Multicentre, Open-label, Phase 3 Trial to Compare the Efficacy and Safety of Lenvatinib (E7080) Versus Sorafenib in First-line Treatment of Participants With Unresectable Hepatocellular Carcinoma  [1]

NCT01761266

Phase

III

Control

Sorafenib

Absolute survival gain

OS gain: 1.3 months

PFS gain: 3.7 months

HR (95% CI)

OS HR: 0.92 (0.79–1.06)

PFS HR: 0.66 (0.57–0.77)

QoL/toxicity

Delayed deterioration

ESMO-MCBS scoreb

4 (Form 2c)

Therapy

Cabozantinib versus placebo in second-line treatment

Disease setting

Second-line unresectable hepatocellular carcinoma after TKI

Trial

Study of Cabozantinib (XL184) vs Placebo in Subjects With Hepatocellular Carcinoma Who Have Received Prior Sorafenib (CELESTIAL) [2]

NCT01908426

Phase

III

Control

Placebo

Absolute survival gain

OS gain: 2.2 months

PFS gain: 3.3 months

HR (95% CI)

OS HR: 0.76 (0.63–0.92)

PFS HR: 0.44 (0.36–0.52)

QoL/toxicity

-

ESMO-MCBS scoreb

3 (Form 2a)

Therapy

Regorafenib after sorafenib in second-line treatment

Disease setting

Second-line unresectable hepatocellular carcinoma after TKI

Trial

Study of Regorafenib After Sorafenib in Patients With Hepatocellular Carcinoma (RESORCE) [3]

NCT01774344

Phase

III

Control

Placebo

Absolute survival gain

OS gain: 2.8 months

2-year survival gain >10%

PFS gain: 1.6 months

HR (95% CI)

OS HR: 0.63 (0.50–0.79)

PFS HR: 0.46 (0.37–0.56)

QoL/toxicity

-

ESMO-MCBS scoreb

4 (Form 2a)

Therapy

Ramucirumab versus placebo in advanced HCC

Disease setting

Patients with advanced HCC or cannot be removed by surgery with a high blood level of AFP and previously treated with sorafenib

Trial

A study of Ramucirumab (LY3009806) Versus Placebo in Participants With Hepatocellular Carcinoma and Elevated Baseline Alpha-Fetoprotein (REACH-2) [4]

NCT02435433

Phase

III

Control

Placebo

OS 7.3 months

Absolute survival gain

OS gain: 1.2 months

HR (95% CI)

OS HR 0.71 (0.53–0.95)

QoL/toxicity

-

ESMO-MCBS scoreb

1 (Form 2a)

aEMA approvals since January 2016.

bESMO-MCBS version 1.1 [5]. The scores have been calculated by the ESMO-MCBS Working Group and validated by the ESMO Guidelines Committee.

AFP, α-fetoprotein; CI, confidence interval; EMA, European Medicines Agency; ESMO-MCBS, Magnitude of Clinical Benefit Scale; HR, hazard ratio; OS, overall survival; PFS, progression-free survival; QoL, quality of life; TKI, tyrosine kinase inhibitor.

References

  1. Kudo M, Finn RS, Qin S et al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet 2018; 391:1163–73.
  2. Abou-Alfa GK, Meyer T, Cheng A-L et al. Cabozantinib in patients with advanced and progressing hepatocellular carcinoma. N Engl J Med 2018; 379: 54–63.
  3. Bruix J, Qin S, Merle P et al. Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 2017; 389: 56–66.
    a randomised phase 3 non-inferiority trial. Lancet 2018; 391: 1163–1173.
  4. Zhu A X, Kang Y-K, Yen C-J et al. Ramucirumab after sorafenib in patients with advanced hepatocellular carcinoma and increased α-fetoprotein concentrations (REACH-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2019; S1470-2045(18)30937-9.
  5. Cherny NI, Dafni U, Bogaerts J et al. ESMO-Magnitude of Clinical Benefit Scale Version 1.1. Ann Oncol 2017; 28: 2340–2366.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings