ASCO GUIDELINES Bundle

Treatment ➤ Recommendation 1.2: Where there are contraindications to atezolizumab and/or bevacizumab, tyrosine kinase inhibitors (TKIs) sorafenib or lenvatinib may be offered as first-line treatment of patients with advanced HCC, Child- Pugh class A, and ECOG PS 0-1 (Strong recommendation; EB-B-M). Qualifying statements: ▶ Treatment with recommended TKIs may be less effective for patients with more advanced liver cirrhosis. Careful patient selection is recommended. ▶ The choice of treatment with lenvatinib or sorafenib should be made through a discussion involving the physician and patient (and caregiver, where applicable) and should include factors such as medical history, viral etiolog y of liver disease, toxicities associated with treatment, cost, goals of treatment, patient preference, and expected treatment benefit. Factors affecting this choice, including response rates, are discussed further in the Clinical Interpretation. ▶ Several meta-analyses of RCTs have shown sorafenib to be more beneficial in patients with HCV, especially as compared with patients with HBV. In the REFLECT trial, there was a trend toward improvements across endpoints for lenvatinib over sorafenib in the HBV subgroup, though it was not significant. ▶ Patients with a high tumor burden, >50% liver involvement, or those with main portal vein invasion were excluded from the REFLECT trial of sorafenib versus lenvatinib. Second-Line Therapy ➤ Recommendation 2.1: Following first-line treatment with atezo + bev, second-line therapy with a TKI (ie, sorafenib, lenvatinib, cabozantinib, or regorafenib) may be recommended (Weak recommendation; IC-B-L). Qualifying statement: ▶ No data have been published on therapy options after first-line treatment with atezo + bev. It is the opinion of the Expert Panel that a TKI, preferably sorafenib or lenvatinib, may be offered. Cabozantinib or regorafenib are also reasonable options for second-line therapy following atezo + bev. ➤ Recommendation 2.2. Following first-line therapy with sorafenib or lenvatinib, second-line therapy with another TKI (cabozantinib or regorafenib), ramucirumab (AFP ≥400 ng/mL), or atezo + bev may be recommended for appropriate candidates. (Considerations regarding choice of therapy are included in the full text Guideline) (Weak recommendation; IC-B-L/M). Qualifying statement: ▶ It is likely that most patients being considered for atezo + bev in the second-line setting did not have access to this combination when they started first-line treatment. ➤ Recommendation 2.3: Following first-line therapy with sorafenib or lenvatinib, pembrolizumab or nivolumab are reasonable options that may be considered for appropriate candidates (Weak recommendation; IC-B-L). Qualifying statement: ▶ Immune checkpoint inhibitors pembrolizumab or nivolumab may be especially beneficial for patients who have contraindications to or cannot tolerate TKIs.

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