<b><i>Background:</i></b> Most phase 3 clinical trials of systemic therapy for first-line unresectable hepatocellular carcinoma (HCC) have failed, with the exception of SHARP, REFLECT, and IMbrave150. We conducted indirect comparisons of therapies evaluated for first-line HCC treatment. <b><i>Summary:</i></b> We conducted a systematic review and meta-analysis of treatments for adults with locally advanced or metastatic unresectable HCC and no prior systemic treatment, including atezolizu­mab plus bevacizumab, sorafenib, lenvatinib, nivolumab, selective internal radiotherapy (SIRT), transarterial chemoembolization, and placebo or best supportive care. Randomized controlled trials published from January 1, 2007, to March 12, 2020, were retrieved from MEDLINE and Embase. Qualitative assessment of heterogeneity evaluated study designs, populations, and outcomes. Indirect comparisons used generalized linear models with random effects within a Bayesian framework and informative priors. We calculated relative efficacy estimates with 95% credible intervals (CrIs) and Bayesian posterior probability estimates of atezolizumab-bevacizumab being superior to other treatments. Nine clinical studies with a total of 3,897 participants were identified from 8,783 records and used to build the all-trials evidence network. Indirect comparisons suggested an improved overall survival (OS) with atezolizumab-bevacizumab versus lenvatinib (odds ratio, 0.63 [95% CrI 0.39–1.04]; with 97% Bayesian posterior probability of being superior), nivolumab (0.68 [95% CrI 0.41–1.14]; 94%), sorafenib (0.59 [95% CrI 0.39–0.87]; 99%), SIRT (0.51 [95% CrI 0.32–0.82]; 100%), or placebo/best supportive care (0.40 [95% CrI 0.25–0.64]; 100%). <b><i>Key Messages:</i></b> Within the context of indirect comparisons, analyses of OS favored atezolizumab-bevacizumab versus other treatment options for patients with locally advanced or metastatic unresectable HCC.

Background Influenza is a persistent public health problem with a significant burden on patients, employers, and society. A systematic review by Keech and Beardsworth (2008) characterized the burden of influenza/influenza-like illness (ILI) on absenteeism. We conducted a systematic literature review evaluating the impact of influenza/ILI on work productivity among adults as an update to the work of Keech and Beardsworth. Methods This systematic review identified studies evaluating the impact of influenza/ILI on absenteeism, presenteeism, or related work productivity measures for employees and employed caregivers based on laboratory confirmation, physician diagnosis, and/or self-reported illness. Eligible studies were in English, French, or German published from 7 March 2007 through 15 February 2022, in PubMed, Embase, or BIOSIS. Two reviewers completed screening and full-text review, with conflicts resolved by a third advisor. Summary data were extracted by two analysts; all records were quality checked by one analyst. Work productivity outcomes were summarized qualitatively, and risk of bias was not evaluated. Results A total of 14,387 records were retrieved; 12,245 titles/abstracts were screened and 145 full-text publications were reviewed, of which 63 were included in the qualitative assessment. Studies of self-reported ILI were most frequent (49%), followed by laboratory-confirmed cases (37%) and physician diagnoses (11%). Overall, approximately 20–75% of employees missed work due to illness across study settings and populations. Mean time out of work among ill employees varied widely across study designs and populations, ranging from < 1 to > 10 days, and was often reported to be approximately 2–3 days. Considerable heterogeneity was observed across study designs, populations, and outcomes. Most employees (≈ 60–80%) reported working while experiencing influenza/ILI symptoms. Reporting of costs was sparse and heterogeneous; one study reported annual costs of influenza-related absences equating to $42,851 per 100,000 employee health plan members. Results were partitioned based on the following categories. Among otherwise healthy adults, 1–74% of workers missed ≥1 workday due to influenza/ILI, for a mean [standard deviation (SD)] of 0.5 (1.44) to 5.3 (4.50) days, and 42–89% reported working while ill, for a mean (SD) of 0.3 (0.63) to 4.4 (3.73) days. Among working caregivers, 50–75% missed work to care for children/household members with influenza/ILI, for 1–2 days on average. Similarly, the mean absenteeism among healthcare workers ranged from 0.5 to 3.2 days. Across studies evaluating vaccination status, generally smaller proportions of vaccinated employees missed time from work due to influenza/ILI. Conclusions This systematic review summarized the productivity burden of influenza/ILI on the worldwide working-age population. Despite notable heterogeneity in study designs, influenza/ILI case definitions, a...

4585 Background: The IMbrave150 pivotal study in unresectable HCC showed superiority of atezolizumab + bevacizumab (atezo + bev) vs sorafenib for OS and PFS. Based on these data supporting first-line atezo + bev for HCC, we conducted a network meta-analysis (NMA) to compare the efficacy of atezo + bev with other systemic and local therapies approved for HCC. Methods: A systematic literature review identified randomized controlled trials in adults with locally advanced or metastatic HCC and no prior systemic therapy for HCC. Studies of therapies now approved for any line of HCC treatment with data reported for first-line treatment since sorafenib approval in 2007 were eligible. Screening of 8783 records yielded 55 trials for inclusion; 9 studies were eligible for the evidence network. Reported hazard ratios (HRs) for OS and PFS were extracted from published studies. The IMbrave150, REFLECT and CheckMate-459 study populations were considered sufficiently similar to compare. A generalized linear model with random effects was used to estimate indirect treatment effects. Informative priors for the heterogeneity of treatment effects across trials were adopted given the limited number of trials to inform each pairwise comparison. HRs with 95% credible intervals (CrIs) and Bayesian posterior probability of atezo + bev being superior to other treatments were calculated for each treatment comparison. The base case NMA compared the relative efficacy of atezo + bev vs sorafenib observed in the IMbrave150 study with the relative effect of other therapies. Sensitivity analyses were performed to compare subgroup results as appropriate based on disease etiology, extrahepatic spread and geography. Results: NMA results suggested improved OS with atezo + bev vs lenvatinib (HR, 0.63; 95% CrI: 0.32, 1.25; probability of atezo + bev being superior to lenvatinib: 93.7%) or nivolumab (HR, 0.68; 95% CrI: 0.35, 1.38; probability of atezo + bev being superior to nivolumab: 90.3%) and improved PFS with atezo + bev vs lenvatinib (HR, 0.91; 95% CrI: 0.23, 3.65; probability of atezo + bev being superior to lenvatinib: 61.5%) or nivolumab (HR, 0.63; 95% CrI: 0.16, 2.59; probability of atezo + bev being superior to nivolumab: 85.5%). Conclusions: This NMA suggested greater OS and PFS benefits with first-line atezo + bev treatment vs other therapies approved for treatment of unresectable HCC.

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Background & aims: The objective of this systematic literature review (SLR) and network meta-analysis (NMA) is to compare randomised controlled trial evidence for atezolizumab-bevacizumab with globally relevant pharmacological comparators for first-line treatment of patients with unresectable hepatocellular carcinoma (HCC). Methods: Randomised controlled trials investigating first-line treatment of HCC in adults with no prior systemic treatment were eligible for inclusion into the SLR and were retrieved from Embase, MEDLINE, and Evidence Based Medicine (EBM) Reviews. Interventions of interest for the NMA included atezolizumab-bevacizumab, sorafenib, lenvatinib, durvalumab (including in combination with tremelimumab), cabozantinib (including in combination with atezolizumab), camrelizumab (including in combination with rivoceranib), pembrolizumab (including in combination with lenvatinib) and tislelizumab. Random effects NMA was conducted for survival endpoints within a Bayesian framework with an informative prior distribution for between study heterogeneity. The hazard ratios for relative treatment effect were estimated with 95% credible intervals (CrIs). Results: The SLR identified 49 studies, of which eight formed a connected evidence network permitting the indirect treatment comparison of atezolizumab-bevacizumab with comparators of interest. The indirect comparisons suggested an improved overall survival (OS) with atezolizumab-bevacizumab versus most comparators. All indirect treatment comparison results for atezolizumab-bevacizumab included the null value within the 95% CrI (n=1) for OS and progression free survival (PFS). Conclusions: The results of the NMA indicate atezolizumab-bevacizumab is associated with superior or comparable OS and PFS together with a manageable safety profile compared with globally relevant comparators in the unresected HCC indication. The findings support that atezolizumab-bevacizumab remains standard of care for the management of first-line unresectable HCC patients.