Would you ever consider using durvalumab/tremelimumab in second line after progression on atezolizumab and bevacizumab in advanced HCC?

This is a really interesting question as primary prospective trials in this setting are limited. Following progression of atezolizumab/bevacizumab, there was a recent abstract of a phase 2 trial using the combination regorafenib + pembrolizumab (N=95 patients, cohort 1 of 68 patients having received atezolizumab/bevacizumab, cohort 2 of 27 patients having received any prior ICI) (El-Khoueiry et al., Journal of Clinical Oncology 2024) showing a PFS of 2.8 months for cohort 1 and 4.2 months for cohort 2. ORR was 5.9% vs 11.1% respectively. This is clearly very modest in terms of benefit in the second line. Whether durvalumab/tremelimumab may have similar or better activity following atezolizumab/bevacizumab is unknown.

Anecdote-wise, I think...

I would consider using durvalumab/tremelimumab in second line after progression on Atezolizumab and Bevacizumab in advanced HCC.

If not previously used, both Category 1, NCCN accepted first-line HCC regimens: atezolizumab plus bevacizumab and trelimumab plus durvalumab are reasonable to consider for subsequent lines of treatment. However, there is no comparative data to define optimal treatment after first-line systemic therapy.

Current guidelines from the American Association for the Study of Liver Diseases, the American Society of Clinical Oncology, and NCCN recommend tyrosine kinase inhibitors (sorafenib, lenvatinib, cabozantinib, or regorafenib) as preferred second-line options, along with ipilimumab plus nivolumab as an alternative for select patients. (Singal et al., PMID 37199193, Gordan et al., PMID 38502889)

While trelimumab plus durvalumab is not a standard r...