Impact of body mass index in patients receiving atezolizumab plus bevacizumab for hepatocellular carcinoma

Abstract

Background Atezolizumab plus bevacizumab (Atezo/Bev) is first line-treatment for unresectable hepatocellular carcinoma (HCC). Body mass index (BMI) has demonstrated predictive value for response to immunotherapy in non-HCC cancer types. Our study investigated the effect of BMI on safety and efficacy of real-life use of Atezo/Bev for unresectable HCC. Methods 191 consecutive patients from seven centres receiving Atezo/Bev were included in the retrospective study. Overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and disease control rate (DCR) defined by RECIST v1.1 were measured in overweight (BMI ≥ 25) and non-overweight (BMI < 25) patients. Treatment-related adverse events (trAEs) were evaluated. Results Patients in the overweight cohort (n = 94) had higher rates of non-alcoholic fatty liver disease (NAFLD) and lower rates of Hepatitis B compared to non-overweight cohort (n = 97). Baseline Child–Pugh class and Barcelona Clinic Liver Cancer stage were similar between cohorts, with lower rates of extrahepatic spread in the overweight group. Overweight patients had similar OS compared to non-overweight (median OS 15.1 vs. 14.9 months; p = 0.99). BMI did not influence median PFS (7.1 vs. 6.1 months; p = 0.42), ORR (27.2% vs. 22.0%; p = 0.44) and DCR (74.1% vs. 71.9%; p = 0.46). There were higher rates of atezolizumab-related fatigue (22.3% vs. 10.3%; p = 0.02) and bevacizumab-related thrombosis (8.5% vs. 2.1%; p = 0.045) in the overweight patients, but overall trAEs and treatment discontinuation were comparable between cohorts. Conclusion Atezo/Bev has comparable efficacy in overweight HCC patients, with an increase in treatment-related fatigue and thrombosis. Combination therapy is safe and efficacious to use in overweight patients, including those with underlying NAFLD.

Impact of body mass index on the prognosis of unresectable HCC patients receiving first‐line Lenvatinib or atezolizumab plus bevacizumab

“…24 On the other hand, Vithayathil and colleagues performed a retrospective analysis in patients who received atezolizumab plus bevacizumab, reporting comparable survival in overweight and non-overweight patients, with the overweight experiencing a higher incidence of fatigue compared to the non-overweight. 25 Differences between the present findings and the previous ones could be ascribed to the differences in both sample sizes and baseline characteristics of the cohorts. In particular, our cohort of patients included both patients who received atezolizumab plus bevacizumab and patients who received lenvatinib; patients who received atezolizumab plus bevacizumab in our cohort were 300 compared to 191 patients included in the analysis of Vithayathil and colleagues.…”

“…In particular, our cohort of patients included both patients who received atezolizumab plus bevacizumab and patients who received lenvatinib; patients who received atezolizumab plus bevacizumab in our cohort were 300 compared to 191 patients included in the analysis of Vithayathil and colleagues. 25 The proportion of patients with a viral hepatopathy was higher in our cohort of patients compared those of the colleagues. These differences, as well as differences in terms of analysis, could explain the different results.…”

“…Moreover, the present analysis did not display differences in terms of incidence of AEs in either of the treatment groups according to the BMI; however, a tendency towards a higher incidence of immunerelated adverse events was documented in underweight compared to normal-weight patients has been highlighted in the atezolizumab plus bevacizumab cohort of patients, which is quite inconsistent with previous data The analysis of Vithayathil and colleagues reported a higher rate of treatment-related fatigue and thrombosis in the overweight patients with a comparable overall rate of AEs and discontinuation in the two groups of patients. 25 Previous data reported a clear association between high BMI and higher rates of treatment-related AEs and treatment discontinuation in several cancer setting. 20,44,45 In addition, Patients with low BMI may correspond, at least to a certain extent, to patients with sarcopenia and cachexia, thus justifying shorter survival in both treatment groups compared with normal and overweight patients.…”

“…24 Contrarily, Vithayathil and colleagues recently reported a comparable efficacy in overweight HCC patients compared to normal weight when receiving atezolizumab plus bevacizumab, with a major incidence of treatment-related fatigue in overweight patients. 25 Unfortunately, these data are not conclusive and deeper investigation on large sample are needed in order to define the role of BMI in this setting of patients.…”

“…Recently, Chen and colleagues retrospectively analysed 101 HCC patients who received immunotherapy, and highlighted that a higher BMI confers better prognosis in terms of both PFS and OS in this setting of patients 24 . Contrarily, Vithayathil and colleagues recently reported a comparable efficacy in overweight HCC patients compared to normal weight when receiving atezolizumab plus bevacizumab, with a major incidence of treatment‐related fatigue in overweight patients 25 . Unfortunately, these data are not conclusive and deeper investigation on large sample are needed in order to define the role of BMI in this setting of patients.…”