Atezolizumab plus bevacizumab and other potential combination therapies will become what I have been calling line minus 1. This will help provide the proven value of sorafenib followed by regorafenib; lenvatinib as first line; ramicirumab as second line if AFP is >400mg/mL; and cabozantinib as se...

This has not been formally answered in clinical studies. However, given lack of prior exposure to a kinase inhibitor, either Sorafenib or Lenvatinib would be reasonable to attempt after first-line Atezolizumab/Bevacizumab. 

While there is no data to guide treatment after atezolizumab and bevacizumab, it is reasonable to use lenvatinib or sorafenib in this setting, with sequencing of other VEGF TKIs (i.e. regorafenib and cabozantinib) subsequent to that.

I would agree that TKI as a second line approach sounds reasonable. However, I am not sure Atezo + Bevacizumab should always be the first line. I even think the overall survival data was not matured. The median follow up for the study as it is published in NEJM was 8.6 months. It was not mentioned ...

If the patient has good access to clinical trials, I would try to fit them in an IO therapy. I have had great success with a patient with Cholangio and HRAS mutation with Second Gen IO therapy. Those patients need to have NGS and look for a potential target, even if you plan to place in a TKI line ...

An interesting paper in the December JAMA Oncology that tries to address this question. Sonbol et al., PMID 33090186