Clinical effects and emerging issues of atezolizumab plus bevacizumab in patients with advanced hepatocellular carcinoma from Japanese real‐world practice

Abstract

Background Although the efficacy of atezolizumab has been demonstrated in randomized controlled trials, its long‐term efficacy and association with adverse events in real‐world practice are unknown. This study was designed to shed light on these issues. Methods In this multicenter retrospective study, data were collected from patients with advanced hepatocellular carcinoma treated with atezolizumab plus bevacizumab in seven institutions in Japan. The authors focused on the efficacy and adverse events related to vascular endothelial growth factor (VEGF) inhibition. Results A total of 123 patients were enrolled in this study. The median progression‐free survival (PFS) for the first‐line treatment group was 8.0 months (95% confidence interval [CI], 6.1–9.9), whereas the median PFS for the second‐ or later‐line treatment group was 4.1 months (95% CI, 2.6–5.7), which was significantly worse than that of the first‐line treatment group (p = .005). Twenty‐seven patients had interrupted bevacizumab treatment. Proteinuria accounted for the largest proportion of bevacizumab treatment interruptions. The cumulative incidence rate of bevacizumab interruption due to anti‐VEGF–related adverse events was significantly higher in patients with hypertension and/or diabetes mellitus than in those without (p = .026). The landmark analysis showed that patients experienced bevacizumab interruption by 24 weeks from treatment initiation had poorer PFS than those who did not (p = .013). Conclusions The PFS of atezolizumab plus bevacizumab as first‐line treatment mostly replicates that of a global phase 3 trial. Interrupted bevacizumab treatment was more common in patients with hypertension and/or diabetes mellitus, which may be associated with worsening long‐term PFS. Plain language summary Atezolizumab plus bevacizumab has been the standard front line systemic therapy for advanced hepatocellular carcinoma. With the growing incidence of fatty liver due to metabolic syndrome as a background liver disease for hepatocellular carcinoma, the rate of comorbid hypertension and diabetes mellitus has been increasing accordingly. The present study demonstrated the cumulative incidence rate of bevacizumab interruption due to anti‐VEGF–related adverse events was significantly higher in patients with hypertension and/or diabetes mellitus. The landmark analysis clarified that interruption of bevacizumab might be a risk of impaired efficacy of atezolizumab plus bevacizumab over the long term in patients with advanced hepatocellular carcinoma.

Impact of first‐line systemic therapy with atezolizumab plus bevacizumab in patients with hepatocellular carcinoma

“…Further, they clarified adverse events for their overall cohort and for IMbrave150 trial “in” and “out” groups separately 35 . The results of this study were generally the same as those of their study 35 and were considered to validate the real‐world outcomes of Atezo/Bev therapy for HCC in Japan. Compared with Nakagawa et al .…”

“…Compared with Nakagawa et al . 's study, 35 the advantage of this study was that it included a larger number of patients with long‐term observation period and their Child–Pugh class was only A disease. Another advantage of this study was that all of our study patients had been evaluated for therapeutic response.…”

“…Nakagawa et al 35 reported that the median progression-free survival for the first-line group was 8.0 months (95% CI, 6.1-9.9), whereas that for the later-line group was 4.1 months (95% CI, 2.6-5.7), which was significantly worse than that of the first-line group (P = 0.005) using the 123 patients with Child-Pugh A and B disease and from multicenter in Japan with median observation period was 7.6 months (7.0-8.2). In addition, they found radiological therapeutic response using 114 (92.7%) patients in their cohort, with an ORR of 15.8% and DCR of 81.6%.…”

“…In addition, they found radiological therapeutic response using 114 (92.7%) patients in their cohort, with an ORR of 15.8% and DCR of 81.6%. 35 Further, they clarified adverse events for their overall cohort and for IMbrave150 trial "in" and "out" groups separately. 35 The results of this study were generally the same as those of their study 35 and were considered to validate the real-world outcomes of Atezo/Bev therapy for HCC in Japan.…”

Exploration of new positions for cabozantinib for advanced hepatocellular carcinoma in the latest real-world practice

“…The clinical course of systemic therapy in patients with advanced HCC primarily starts with combined immunotherapy, followed by sequencing of molecular-targeted agents [21]. Many molecular-targeted agents, when utilized in late-line settings, have been found to have reduced therapeutic e cacy and a high AE discontinuation rate [22,23]. Even for patients with poor liver function or at the late line, cabozantinib might be an encouraging option, as it has shown adequate e cacy to boost the likelihood of long-term treatment with careful dose reduction initiation.…”