Efficacy and safety of atezolizumab plus bevacizumab in patients with portal hypertension for unresectable hepatocellular carcinoma

Abstract

Aim: Atezolizumab plus bevacizumab combination therapy (Atezo + Beva) is used as the first-line therapy for unresectable hepatocellular carcinoma (u-HCC). Serious adverse events (AEs), including rupture of esophagogastric varices, have been seen during treatment. Therefore, the relationships of efficacy, safety, and portal hypertension (PH) were analyzed.

Methods: A total of 146 patients with u-HCC and Child-Pugh Scores of 5-7 received Atezo + Beva. Prophylactic treatment for varices was performed for patients with the risk of rupture of varices before the start of Atezo + Beva. A propensity score-matched cohort was created to minimize the risk of potential confounders. Efficacy was assessed in 41 propensity score-matched pairs. AEs were assessed between patients without PH (n = 80) and with PH (n = 66).

Results: In patients without PH and with PH, median overall survival was 18.4 months and 18.8 months (p = 0.71), and median progression-free survival was 8.6 months and 5.8 months (p = 0.92), respectively. On the best radiological response evaluation for Response Evaluation Criteria in Solid Tumors, the objective response rate was 31.7% and 26.8% (p = 0.81), respectively. Variceal rupture occurred in three patients with PH, but there were no significant differences in the occurrence of variceal rupture (p = 0.090) and Grade 3-4 AEs between patients without and with PH.

Conclusions: No significant differences in efficacy and safety were observed with PH. Prophylactic treatment for varices before the start of Atezo + Beva would allow treatment to continue relatively safely.

Keywords: adverse events; atezolizumab plus bevacizumab; esophagogastric variceal rupture; hepatocellular carcinoma; portal hypertension.

FIGURE 1

Flow chart of endoscopic evaluation of esophageal varices (EV) and gastric varices (GV) before the start of atezolizumab plus bevacizumab combination therapy (Atezo + Beva). F, form; RC, red color sign.

FIGURE 2

The method for measuring the volume of the spleen using maximal length (Lmax) in the axial image and vertical height (Hvert) in the coronal image.

FIGURE 3

Diagram of the numbers of patients with varices, splenomegaly, and portosystemic collateral vessels at the start of atezolizumab plus bevacizumab combination therapy.

FIGURE 4

Comparison of overall survival (OS) and progression‐free survival (PFS) from the start of atezolizumab plus bevacizumab (Atezo + Beva) between patients without portal hypertension (PH(−)) and with portal hypertension (PH(+)) after propensity score matching. (A) OS from the start of Atezo + Beva (PH(−) 18.4 months, PH(+) 18.8 months, p = 0.71). (B) PFS from the start of Atezo + Beva (PH(−) 8.6 months, PH(+) 5.8 months, p = 0.92).

FIGURE 5

Flow chart of the numbers of patients with portal hypertension with varices, treatment of varices, and rupture. B‐RTO, balloon‐occluded retrograde transvenous obliteration; EIS, endoscopic injection sclerotherapy; EV, esophageal varices; EVL, endoscopic variceal ligation; GV, gastric varices.