{"entity":{"id":"paper-imbrave150-nejm-2020","kind":"paper","name":"IMbrave150: atezolizumab plus bevacizumab replaces sorafenib as first treatment for advanced liver cancer","aka":[],"tldr":"Combining the immunotherapy atezolizumab with the anti-blood-vessel antibody bevacizumab helped patients with advanced hepatocellular carcinoma live longer than sorafenib, ending a decade in which nothing had beaten that drug.","summary":"Open-label phase 3 trial of 501 patients with unresectable hepatocellular carcinoma and preserved liver function (Child-Pugh A) who had not received systemic therapy, randomised 2:1 to atezolizumab plus bevacizumab or sorafenib. Co-primary endpoints were OS and PFS.\n\n12-month OS was 67.2% vs 54.6% (HR 0.58) and median PFS 6.8 vs 4.3 months (HR 0.59). The updated analysis showed median OS 19.2 vs 13.4 months (HR 0.66). It made atezolizumab plus bevacizumab the first-line standard, showed that immunotherapy combinations can work in liver cancer despite the failure of single-agent checkpoint inhibitors, and set the template for durvalumab plus tremelimumab (HIMALAYA).","asOf":"2026-09-08","links":[{"label":"NEJM 2020","url":"https://doi.org/10.1056/NEJMoa1915745"},{"label":"ClinicalTrials.gov NCT03434379","url":"https://clinicaltrials.gov/study/NCT03434379"}],"tags":[],"related":[],"cancers":["hcc"],"sections":[],"technologies":["checkpoint-inhibitor","antiangiogenic","monoclonal-antibody"],"targets":["pdl1","vegf"],"drugs":["atezolizumab"],"companies":["roche-genentech"],"institutions":[],"pathways":[],"terms":["os","pfs","first-line","standard-of-care"],"trials":[],"people":["kim-tae-you","lim-ho-yeong"],"bottlenecks":["b-immunotherapy-response","b-global-access","b-combination-space"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2020,"doi":"10.1056/NEJMoa1915745","authors":"Finn RS, Qin S, Ikeda M, et al.","paperType":"rct","findings":["12-month overall survival 67.2% vs 54.6%; HR 0.58 (95% CI 0.42-0.79).","Median PFS 6.8 vs 4.3 months; HR 0.59.","Objective response 27.3% vs 11.9% (RECIST 1.1).","Updated analysis (2022): median OS 19.2 vs 13.4 months, HR 0.66; median PFS 6.9 vs 4.3 months.","Grade 3-4 adverse events similar (57% vs 55%); upper gastrointestinal bleeding with bevacizumab required endoscopic screening for varices within six months before enrolment.","Patient-reported quality of life deteriorated later with the combination (11.2 vs 3.6 months)."],"whatItMeans":"Patients with advanced liver cancer and good liver function should be offered atezolizumab plus bevacizumab (or durvalumab plus tremelimumab) rather than sorafenib as first treatment; median survival is now around 19 months and about a quarter of patients respond. Endoscopy to treat varices before starting bevacizumab is essential because of bleeding risk. Patients with poorer liver function (Child-Pugh B) or autoimmune disease or transplants were not studied.","caveats":["Excluded Child-Pugh B, untreated varices, and prior transplant, so applies to a selected population.","Open-label; sorafenib is now a weak comparator.","Non-viral (metabolic) liver cancer appeared to benefit less in exploratory analyses across several immunotherapy trials.","Bleeding and hypertension from bevacizumab, and cost, remain barriers in high-incidence low-income regions."],"changedPractice":true,"participants":501},"route":"/key-papers/paper-imbrave150-nejm-2020/","neighbours":{"cancer":[{"id":"hcc-advanced","kind":"cancer","name":"Advanced hepatocellular carcinoma (BCLC C)","route":"/cancers/hcc-advanced/"},{"id":"hcc","kind":"cancer","name":"Hepatocellular carcinoma","route":"/cancers/hcc/"}],"technology":[{"id":"antiangiogenic","kind":"technology","name":"Anti-angiogenic therapy","route":"/technologies/antiangiogenic/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"},{"id":"monoclonal-antibody","kind":"technology","name":"Monoclonal antibodies","route":"/technologies/monoclonal-antibody/"}],"target":[{"id":"pdl1","kind":"target","name":"PD-L1","route":"/targets/pdl1/"},{"id":"vegf","kind":"target","name":"VEGF / VEGFR","route":"/targets/vegf/"}],"drug":[{"id":"atezolizumab","kind":"drug","name":"Atezolizumab","route":"/drugs/atezolizumab/"}],"company":[{"id":"roche-genentech","kind":"company","name":"Roche / Genentech","route":"/companies/roche-genentech/"}],"term":[{"id":"first-line","kind":"term","name":"Lines of therapy","route":"/terms/first-line/"},{"id":"os","kind":"term","name":"Overall survival (OS)","route":"/terms/os/"},{"id":"pfs","kind":"term","name":"Progression-free survival (PFS)","route":"/terms/pfs/"},{"id":"standard-of-care","kind":"term","name":"Standard of care","route":"/terms/standard-of-care/"}],"person":[{"id":"ann-lii-cheng","kind":"person","name":"Ann-Lii Cheng","route":"/people/ann-lii-cheng/"},{"id":"lim-ho-yeong","kind":"person","name":"Ho Yeong Lim","route":"/people/lim-ho-yeong/"},{"id":"richard-finn","kind":"person","name":"Richard S. Finn","route":"/people/richard-finn/"},{"id":"kim-tae-you","kind":"person","name":"Tae-You Kim","route":"/people/kim-tae-you/"}],"bottleneck":[{"id":"b-global-access","kind":"bottleneck","name":"Most of the world has almost no cancer care","route":"/bottlenecks/b-global-access/"},{"id":"b-immunotherapy-response","kind":"bottleneck","name":"No one can predict who responds to immunotherapy","route":"/bottlenecks/b-immunotherapy-response/"},{"id":"b-combination-space","kind":"bottleneck","name":"Too many combinations to test","route":"/bottlenecks/b-combination-space/"}],"journal":[{"id":"nejm","kind":"journal","name":"New England Journal of Medicine","route":"/journals/nejm/"}],"idea":[{"id":"idea-hcc-io-before-transplant","kind":"idea","name":"Immunotherapy downstaging to transplant with a safe washout","route":"/ideas/idea-hcc-io-before-transplant/"}]}}