Systemic therapy HCC ASCO update

1. Child's pugh A-- durva treme or atezo - bev. Screen for esophageal varices. Screen for autoimmune diseases.

2. First line: If cannot do durva treme or atezo bv, consider lenvatinib, sorafenib or durvalumab. Len is non inferior to sorafenib but with more SE.

3.  After first line as above, 2L- sorafenib, lenvatinib, cabozantinib, ramucirumab if AFP > 400. Ipi+nivo 2L based on case series. No high quality data, but durva treme can be used 2L following 1st line atezo bev.

4. 2L following 1st line TKI- cabozantinib, regorafenib. Can do single agent IO pembro or nivo or front line IO combinations if no contraindications.

5. Child Pugh class B- benefit is modest at best with standard rx as listed above. Shared decision making encouraged. Sorafenib in non SHARP trial pt is similar to best  supportive care. The toxicity of sorafenib was similar whether Child's A or Child's B.

6. Prognosis: Durva treme HIMALAYA median OS 16 months; Atezo bev median OS 13 months.

7. Main side effects  : hand foot syndrome higher with TKI. HTN. elevated AST. Diarrhea. All more common with sorafenib except HTN with atezo bev. Proteinuria. Elevated lipase and bilirubin. Alopecia with sorafenib.

8. Most studies exclude macrovascular portal vein invasion and > 50% hepatic disease burden.

9. Lenvatinib with TACE 1st line, China only, superior OS and PFS compared to len alone. LFT elevation more common with the combination.

10. Ramucirumab in REACH, REACH -2 studies showed OS benefit if AFP> 400 compared to placebo. HTN, hyponatremia were SE.

11. Regorafenib FDA approved 2L for those who progressed on sorafenib baased on RESORCE trial. Only try this if pt is Child Pugh A and was able to tolerate sorafenib 400 mg for 3 weeks or longer. This is not a good drug for those who were intolerant to sorafenib due to greater toxicities. On the other hand cabozantinib is an option if intolerant to sorafenib.

12. Cabozantinib , CELESTIAL trial can be used in 3rd line. 

13. Factors to consider when choosing rx for advanced HCC: performance status, Child's Pugh score, bleeding risk, portal hypertension, esophageal varices, tumor burden, extra hepatic spread and major vascular invasion.

14. Checkmate 040- nivo child Pugh B OS 7.6 months