Immunotherapies now firmly feature in ESMO recommendations for the first-line treatment of advanced hepatocellular carcinoma (HCC).
The Clinical Practice Guideline compiled by a group of international experts contains a raft of new recommendations driven by key advances in the diagnosis and management of the disease since the last version was published in 2018.
For advanced HCC, atezolizumab/bevacizumab and durvalumab/tremelimumab are newly recommended as first-line targeted therapies for patients with well-preserved liver function and ECOG PS 0-1, according to the paper, published in Annals of Oncology [link here].
Atezolizumab/bevacizumab was the first treatment regimen to show a survival advantage over previous standard of care sorafenib, with data from the IMbrave150 trial showing median overall survival (OS) of 19.2 months versus 13.4 months, respectively (HR 0.66), the authors noted.
Improved median OS versus sorafenib was also demonstrated with the single tremelimumab regular interval durvalumab (STRIDE) regimen (single tremelimumab 300mg plus durvalumab 1500mg every four weeks) in the HIMALAYA trial, at 16.4 versus 13.8 months, respectively (HR 0.78), they said.
The guideline group also backed use of camrelizumab/rivoceranib or nivolumab/ipilimumab as first-line treatment options for advance disease.
Clinical trial evidence showed a significant improvement in median OS with the camrelizumab/rivoceranib regimen compared to sorafenib (23.8 versus 15.2 months; HR 0.64), as well as for nivolumab/ipilimumab versus sorafenib or lenvatinib (23.7 versus 20.6 months, respectively; HR 0.79).
In addition, durvalumab/tislelizumab should be considered for patients with contraindications to immune checkpoint inhibitor (ICI) combination therapies, and lenvatinib or sorafenib for those unable to take ICI therapy.
Aside from the addition of sorafenib and lenvatinib as options, the recommendations for the second-line treatment of advanced HCC remain largely unchanged from those issued in 2018 [link here].
Regorafenib or cabozantinib should be considered for patients with well-preserved liver function and ECOG PS 0-1 and disease progression on one or more systemic therapy, while ramucirumab can be considered for patients with AFP ≥400 ng/ml.
Sorafenib should be considered after first-line lenvatinib, and both sorafenib and lenvatinib can be used after first-line ICI therapy, although lenvatinib is not approved for this use, the group noted.
Early/intermediate stage disease
With regard to early or intermediate stage disease, the guideline authors emphasised the importance of MDT management to improving HCC outcomes, taking into account “anatomical complexity, comorbidities, underlying liver dysfunction and heterogeneous tumour biology”.
A variety of potentially curative treatment modalities, such as liver resection, liver transplant and local thermal and radiation ablative therapies, were recommended for HCC patients in certain clinical scenarios.
For example, liver resection was recommended for patients with a single tumour greater than 2 cm and no evidence of portal hypertension, and as an option for patients with intermediate-stage HCC who are unsuitable for intra-arterial therapies.
Also, segmental transarterial therapies can be an alternative option for patients with a single tumour of up to 8 cm who are unable to undergo resection.
They can also be considered in combination with durvalumab/bevacizumab or pembrolizumab/lenvatinib for patients with intermediate-stage disease, although the authors emphasised that the long-term benefit of these combinations is yet to be established.
Click here to read the recommendations in full