Early bevacizumab dose and time modifications may affect efficacy of atezolizumab plus bevacizumab for advanced hepatocellular carcinoma treatment
Background: Atezolizumab (1200 mg) plus bevacizumab (15 mg/kg) every 3 weeks (AtezBev) became a standard-of-care first-line treatment for advanced hepatocellular carcinoma (aHCC) following IMbrave150. However, real-world data suggest milder efficacy. Early bevacizumab interruption due to adverse eve...
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Elsevier
2025-06-01
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| Series: | ESMO Gastrointestinal Oncology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S294981982500055X |
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| author | F. Rossari D. Lavacchi E. Alimenti C. Soldà F. Salani L. Esposito S. Foti S. Camera M. Persano F. Lo Prinzi F. Vitiello E. Pellegrini M. Bruccoleri M.D. Rizzato M. Caccese I.G. Rapposelli A. Guidolin A. De Rosa L. Antonuzzo G. Masi M.A. Iavarone S. Lonardi M. Rimini A. Casadei-Gardini |
| author_facet | F. Rossari D. Lavacchi E. Alimenti C. Soldà F. Salani L. Esposito S. Foti S. Camera M. Persano F. Lo Prinzi F. Vitiello E. Pellegrini M. Bruccoleri M.D. Rizzato M. Caccese I.G. Rapposelli A. Guidolin A. De Rosa L. Antonuzzo G. Masi M.A. Iavarone S. Lonardi M. Rimini A. Casadei-Gardini |
| author_sort | F. Rossari |
| collection | DOAJ |
| description | Background: Atezolizumab (1200 mg) plus bevacizumab (15 mg/kg) every 3 weeks (AtezBev) became a standard-of-care first-line treatment for advanced hepatocellular carcinoma (aHCC) following IMbrave150. However, real-world data suggest milder efficacy. Early bevacizumab interruption due to adverse events (AEs) is a frequent occurrence in real-world scenario associated with poor prognosis. Additionally, early bevacizumab dose/time modifications (eBEVmod) may negatively impact outcome. Materials and methods: Data from AtezBev-treated aHCC patients (n = 100) in five Italian institutions were retrospectively analyzed. Cumulative bevacizumab dose (mg/kg) received in the first 3 months of treatment was analyzed by receiver operating characteristic (ROC) to identify a cut-off value to estimate survival and dichotomize the variable. Baseline clinical and laboratory characteristics were analyzed with uni-/multivariate models to explore potential differences on overall survival (OS), objective response rate (ORR) and disease control rate (DCR) based on eBEVmod. Progression-free survival (PFS) was a secondary endpoint. Results: In the overall population, the median (m) follow-up was 11.4 months, mOS was 20.5 months, mPFS was 10.4 months, ORR was 31% and DCR was 75%. ROC on 3-month cumulative bevacizumab dose revealed an area under the curve of 0.74 (P = 0.001) and eBEVmod cut-off of <45 mg/kg/3 months (i.e. 10.5 mg/kg/3 weeks) having 73% sensitivity and specificity in predicting death. Twenty-three percent of patients had eBEVmod (of which 39.1% had treatment delay, 39.1% discontinuation and 21.7% dose reduction), with no differences in baseline characteristics nor second-line treatments compared with non-eBEVmod, except for sex. eBEVmod patients had inferior ORR/DCR (14%/48% versus 36%/82%) and increased risk of death [hazard ratio (HR) 4.2, P = 0.0049], with a 12-month survival probability of 53.3% versus 77.4%. eBEVmod was an independent negative prognostic factor of survival at multivariate analysis (HR 3.3, P = 0.0125). Patients with eBEVmod also had a trend in worse PFS, although not statistically significant (mPFS 3.8 versus 12.6 months, HR 1.8, P = 0.0774). Conclusions: eBEVmod is an independent unfavorable prognostic factor of response and survival in AtezBev-treated aHCC patients. Optimization of bevacizumab AE management to reduce eBEVmod may substantially improve treatment outcome in real-world practice. |
| format | Article |
| id | doaj-art-ea46ba3694c742bd94853f8da38c2ffa |
| institution | OA Journals |
| issn | 2949-8198 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | ESMO Gastrointestinal Oncology |
| spelling | doaj-art-ea46ba3694c742bd94853f8da38c2ffa2025-08-20T02:07:20ZengElsevierESMO Gastrointestinal Oncology2949-81982025-06-01810018610.1016/j.esmogo.2025.100186Early bevacizumab dose and time modifications may affect efficacy of atezolizumab plus bevacizumab for advanced hepatocellular carcinoma treatmentF. Rossari0D. Lavacchi1E. Alimenti2C. Soldà3F. Salani4L. Esposito5S. Foti6S. Camera7M. Persano8F. Lo Prinzi9F. Vitiello10E. Pellegrini11M. Bruccoleri12M.D. Rizzato13M. Caccese14I.G. Rapposelli15A. Guidolin16A. De Rosa17L. Antonuzzo18G. Masi19M.A. Iavarone20S. Lonardi21M. Rimini22A. Casadei-Gardini23Department of Oncology, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute Hospital, Milan, ItalyClinical Oncology Unit, Careggi University Hospital, Florence, ItalyDivision of Gastroenterology and Hepatology, Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, ItalyMedical Oncology 1, Veneto Institute of Oncology IOV—IRCCS, Padua, ItalyUnit of Medical Oncology 2, University Hospital of Pisa, Pisa, ItalyDepartment of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) ‘Dino Amadori’, Meldola, ItalyDepartment of Oncology, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute Hospital, Milan, ItalyDepartment of Oncology, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute Hospital, Milan, ItalyDepartment of Oncology, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute Hospital, Milan, ItalyDepartment of Oncology, Campus Bio-Medico, Rome, ItalyDepartment of Oncology, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute Hospital, Milan, ItalyClinical Oncology Unit, Careggi University Hospital, Florence, ItalyDivision of Gastroenterology and Hepatology, Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, ItalyMedical Oncology 1, Veneto Institute of Oncology IOV—IRCCS, Padua, ItalyUnit of Medical Oncology 2, University Hospital of Pisa, Pisa, ItalyDepartment of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) ‘Dino Amadori’, Meldola, ItalyClinical Oncology Unit, Careggi University Hospital, Florence, ItalyMedical Oncology 1, Veneto Institute of Oncology IOV—IRCCS, Padua, Italy; Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, ItalyClinical Oncology Unit, Careggi University Hospital, Florence, ItalyUnit of Medical Oncology 2, University Hospital of Pisa, Pisa, ItalyDivision of Gastroenterology and Hepatology, Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy; CRC ‘A. M. and A. Migliavacca’ Center for Liver Disease, Department of Pathophysiology and Transplantation, University of Milan, Milan, ItalyMedical Oncology 1, Veneto Institute of Oncology IOV—IRCCS, Padua, ItalyDepartment of Oncology, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute Hospital, Milan, ItalyDepartment of Oncology, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute Hospital, Milan, Italy; Correspondence to: Prof. Andrea Casadei-Gardini, Università Vita-Salute San Raffaele, IRCCS San Raffaele Hospital, via Olgettina 60, 20132 Milan, Italy. Tel: +39 0226431Background: Atezolizumab (1200 mg) plus bevacizumab (15 mg/kg) every 3 weeks (AtezBev) became a standard-of-care first-line treatment for advanced hepatocellular carcinoma (aHCC) following IMbrave150. However, real-world data suggest milder efficacy. Early bevacizumab interruption due to adverse events (AEs) is a frequent occurrence in real-world scenario associated with poor prognosis. Additionally, early bevacizumab dose/time modifications (eBEVmod) may negatively impact outcome. Materials and methods: Data from AtezBev-treated aHCC patients (n = 100) in five Italian institutions were retrospectively analyzed. Cumulative bevacizumab dose (mg/kg) received in the first 3 months of treatment was analyzed by receiver operating characteristic (ROC) to identify a cut-off value to estimate survival and dichotomize the variable. Baseline clinical and laboratory characteristics were analyzed with uni-/multivariate models to explore potential differences on overall survival (OS), objective response rate (ORR) and disease control rate (DCR) based on eBEVmod. Progression-free survival (PFS) was a secondary endpoint. Results: In the overall population, the median (m) follow-up was 11.4 months, mOS was 20.5 months, mPFS was 10.4 months, ORR was 31% and DCR was 75%. ROC on 3-month cumulative bevacizumab dose revealed an area under the curve of 0.74 (P = 0.001) and eBEVmod cut-off of <45 mg/kg/3 months (i.e. 10.5 mg/kg/3 weeks) having 73% sensitivity and specificity in predicting death. Twenty-three percent of patients had eBEVmod (of which 39.1% had treatment delay, 39.1% discontinuation and 21.7% dose reduction), with no differences in baseline characteristics nor second-line treatments compared with non-eBEVmod, except for sex. eBEVmod patients had inferior ORR/DCR (14%/48% versus 36%/82%) and increased risk of death [hazard ratio (HR) 4.2, P = 0.0049], with a 12-month survival probability of 53.3% versus 77.4%. eBEVmod was an independent negative prognostic factor of survival at multivariate analysis (HR 3.3, P = 0.0125). Patients with eBEVmod also had a trend in worse PFS, although not statistically significant (mPFS 3.8 versus 12.6 months, HR 1.8, P = 0.0774). Conclusions: eBEVmod is an independent unfavorable prognostic factor of response and survival in AtezBev-treated aHCC patients. Optimization of bevacizumab AE management to reduce eBEVmod may substantially improve treatment outcome in real-world practice.http://www.sciencedirect.com/science/article/pii/S294981982500055XHCCatezolizumabbevacizumabimmunotherapydose modification |
| spellingShingle | F. Rossari D. Lavacchi E. Alimenti C. Soldà F. Salani L. Esposito S. Foti S. Camera M. Persano F. Lo Prinzi F. Vitiello E. Pellegrini M. Bruccoleri M.D. Rizzato M. Caccese I.G. Rapposelli A. Guidolin A. De Rosa L. Antonuzzo G. Masi M.A. Iavarone S. Lonardi M. Rimini A. Casadei-Gardini Early bevacizumab dose and time modifications may affect efficacy of atezolizumab plus bevacizumab for advanced hepatocellular carcinoma treatment ESMO Gastrointestinal Oncology HCC atezolizumab bevacizumab immunotherapy dose modification |
| title | Early bevacizumab dose and time modifications may affect efficacy of atezolizumab plus bevacizumab for advanced hepatocellular carcinoma treatment |
| title_full | Early bevacizumab dose and time modifications may affect efficacy of atezolizumab plus bevacizumab for advanced hepatocellular carcinoma treatment |
| title_fullStr | Early bevacizumab dose and time modifications may affect efficacy of atezolizumab plus bevacizumab for advanced hepatocellular carcinoma treatment |
| title_full_unstemmed | Early bevacizumab dose and time modifications may affect efficacy of atezolizumab plus bevacizumab for advanced hepatocellular carcinoma treatment |
| title_short | Early bevacizumab dose and time modifications may affect efficacy of atezolizumab plus bevacizumab for advanced hepatocellular carcinoma treatment |
| title_sort | early bevacizumab dose and time modifications may affect efficacy of atezolizumab plus bevacizumab for advanced hepatocellular carcinoma treatment |
| topic | HCC atezolizumab bevacizumab immunotherapy dose modification |
| url | http://www.sciencedirect.com/science/article/pii/S294981982500055X |
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