Dataset Information

Adverse Events as Potential Predictive Factors of Activity in Patients with Advanced HCC Treated with Atezolizumab Plus Bevacizumab.

ABSTRACT:

Background

In the context of patients with hepatocellular carcinoma (HCC) treated with systemic therapy, the correlation between the appearance of adverse events (AEs) and reported efficacy outcomes is well-known and widely investigated. From other pathological settings, we are aware of the prognostic and predictive value of the occurrence of immune-related AEs in patients treated with immune-checkpoint inhibitors.

Objective

This retrospective multicenter real-world study aims to investigate the potential prognostic value of AEs in patients with HCC treated with atezolizumab plus bevacizumab in the first-line setting.

Patients and methods

The study population consisted of 823 patients from five countries (Italy, Germany, Portugal, Japan, and the Republic of Korea).

Results

Of the patients, 73.3% presented at least one AE during the study period. The most common AEs were proteinuria (29.6%), arterial hypertension (27.2%), and fatigue (26.0%). In all, 17.3% of the AEs were grade (G) 3. One death due to bleeding was reported. The multivariate analysis confirmed the appearance of decreased appetite G < 2 [versus G ≥ 2; hazard ratio (HR) 0.60; 95% confidence interval (CI) 0.13-0.90; p < 0.01] and immunotoxicity G < 2 (versus G ≥ 2; HR: 0.70; 95% CI 0.24-0.99; p = 0.04) as independent prognostic factors for overall survival, and the appearance of decreased appetite G < 2 (versus G ≥ 2; HR: 0.73; 95% CI 0.43-0.95; p = 0.01), diarrhea (yes versus no; HR: 0.57, 95% CI 0.38-0.85; p = 0.01), fatigue (yes versus no; HR: 0.82, 95% CI 0.65-0.95; p < 0.01), arterial hypertension G < 2 (versus G ≥ 2; HR: 0.68, 95% CI 0.52-0.87; p < 0.01), and proteinuria (yes versus no; HR: 0.79, 95% CI 0.64-0.98; p = 0.03) as independent prognostic factors for progression-free survival.

Conclusions

As demonstrated for other therapies, there is also a correlation between the occurrence of AEs and outcomes for patients with HCC for the combination of atezolizumab plus bevacizumab.

SUBMITTER: Persano M

PROVIDER: S-EPMC11230956 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature

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Publications

Adverse Events as Potential Predictive Factors of Activity in Patients with Advanced HCC Treated with Atezolizumab Plus Bevacizumab.

Persano Mara M Rimini Margherita M Tada Toshifumi T Suda Goki G Shimose Shigeo S Kudo Masatoshi M Rossari Federico F Yoo Changhoon C Cheon Jaekyung J Finkelmeier Fabian F Lim Ho Yeong HY Presa José J Masi Gianluca G Bergamo Francesca F Amadeo Elisabeth E Vitiello Francesco F Kumada Takashi T Sakamoto Naoya N Iwamoto Hideki H Aoki Tomoko T Chon Hong Jae HJ Himmelsbach Vera V Iavarone Massimo Alberto MA Cabibbo Giuseppe G Montes Margarida M Foschi Francesco Giuseppe FG Vivaldi Caterina C Soldà Caterina C Sho Takuya T Niizeki Takashi T Nishida Naoshi N Steup Christoph C Bruccoleri Mariangela M Hirooka Masashi M Kariyama Kazuya K Tani Joji J Atsukawa Masanori M Takaguchi Koichi K Itobayashi Ei E Fukunishi Shinya S Tsuji Kunihiko K Ishikawa Toru T Tajiri Kazuto K Ochi Hironori H Yasuda Satoshi S Toyoda Hidenori H Ogawa Chikara C Nishimura Takashi T Hatanaka Takeshi T Kakizaki Satoru S Shimada Noritomo N Kawata Kazuhito K Hiraoka Atsushi A Tada Fujimasa F Ohama Hideko H Nouso Kazuhiro K Morishita Asahiro A Tsutsui Akemi A Nagano Takuya T Itokawa Norio N Okubo Tomomi T Imai Michitaka M Kosaka Hisashi H Naganuma Atsushi A Koizumi Yohei Y Nakamura Shinichiro S Kaibori Masaki M Iijima Hiroko H Hiasa Yoichi Y Foti Silvia S Camera Silvia S Piscaglia Fabio F Scartozzi Mario M Cascinu Stefano S Casadei-Gardini Andrea A

Targeted oncology 20240430 4

<h4>Background</h4>In the context of patients with hepatocellular carcinoma (HCC) treated with systemic therapy, the correlation between the appearance of adverse events (AEs) and reported efficacy outcomes is well-known and widely investigated. From other pathological settings, we are aware of the prognostic and predictive value of the occurrence of immune-related AEs in patients treated with immune-checkpoint inhibitors.<h4>Objective</h4>This retrospective multicenter real-world study aims to ...[more]

PMID: 38689194

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Project description:IntroductionThe phase III IMbrave150 study established atezolizumab + bevacizumab as the global standard of care in patients with unresectable hepatocellular carcinoma (HCC). This exploratory analysis examined the impact of bevacizumab interruption due to bevacizumab adverse events of special interest (AESIs).MethodsPatients in IMbrave150 who were randomized to atezolizumab + bevacizumab and received treatment for ≥6 months (to reduce immortal time bias) were included in group A-1 if bevacizumab had ever been skipped due to bevacizumab AESIs or to group A-2 otherwise. Efficacy analyses included overall survival (OS) and progression-free survival (PFS) by whether bevacizumab was skipped (group A-1 vs. A-2). PFS was evaluated per independent review facility (IRF)-assessed Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1 and HCC-modified RECIST (IRF-HCC mRECIST). Safety was also evaluated.ResultsOf the 210 patients who received ≥6 months of atezolizumab + bevacizumab, 69 were assigned to group A-1 and 141 to A-2. At data cutoff (August 20, 2020), hazard ratio (HR) for OS was 1.04 (95% CI: 0.64, 1.69) for group A-1 versus A-2. HR for PFS was 1.07 (95% CI: 0.74, 1.55) per IRF-assessed RECIST 1.1 and 1.10 (95% CI: 0.76, 1.59; 15.5 vs. 9.7 months) per IRF-HCC mRECIST for group A-1 versus A-2. Safety profiles for atezolizumab and bevacizumab were largely similar between groups. More group A-1 patients had grade 3/4 adverse events. A separate analysis investigating the impact of immortal time bias in patients who received ≥3 months of atezolizumab + bevacizumab supported the appropriateness of the ≥6-month landmark analysis.Discussion/conclusionEfficacy was similar between patients who skipped bevacizumab due to bevacizumab AESIs and those who did not. Although this comparison was nonrandomized and exploratory, results suggest that skipping bevacizumab due to bevacizumab AESIs did not considerably impact the efficacy and safety of atezolizumab + bevacizumab.

Project description:Background & aimsAtezolizumab/bevacizumab (A/B) is now a standard first-line treatment for advanced hepatocellular carcinoma (HCC), but the optimal second-line regimen is not known. We evaluated real-world treatment patterns and outcomes to investigate factors associated with post-progression survival (PPS).MethodsIn this multicenter, international, retrospective study, we examined clinical characteristics and outcomes of patients with advanced HCC who progressed on first-line A/B. The primary outcome of PPS was defined as time from first radiographic progression on A/B to death.ResultsA total of 406 patients alive after progression on first-line A/B were included in the final analysis, of whom 45.3% (n = 184) received best supportive treatment (BST) and 54.7% (n = 222) continued active systemic treatment. In the second line, 155 patients were treated with tyrosine kinase inhibitors (TKIs), 45 with immune checkpoint inhibitor (IO)-based regimens, and 3 had missing data. Median PPS of the whole cohort (mPPS) was 6.0 months (95% CI 5.2-7.2). On multivariate Cox regression analysis, absence of portal vein tumor thrombus, ECOG <2, and continued active treatment were predictors of better PPS. mPPS was significantly longer for patients who continued active treatment vs. BST (9.7 vs. 2.6 months; HR 0.41, p <0.001). In the second-line setting, patients treated with TKIs had a numerically shorter mPPS compared to those treated with IO (8.4 vs. 14.9 months; HR 1.37, p = 0.256).ConclusionsContinuation of active therapy after A/B progression was independently associated with better survival even after adjusting for baseline disease characteristics. mPPS with IO-based therapy exceeded a year, suggesting that IO continuation post-progression may retain benefit. The precise sequencing of TKI and IO regimens warrants further investigation.Impact and implicationsThere is currently a lack of level 1 data on second-line treatment options for patients with advanced hepatocellular carcinoma who progress after frontline atezolizumab plus bevacizumab, as all second-line approvals were established during the frontline sorafenib era. Our study aims to fill in some of the knowledge gap by investigating real-world patient outcomes in the second-line treatment setting. Findings from this study show that patients who continued active treatment had improved post-progression survival compared to those who received best supportive care, and medication regimens incorporating tyrosine kinase inhibitors as well as immunotherapy agents were active. These results can help inform clinicians of possible treatment options for patients who progress after frontline atezolizumab plus bevacizumab while we await maturing data from randomized-controlled trials.

Dataset Information

Adverse Events as Potential Predictive Factors of Activity in Patients with Advanced HCC Treated with Atezolizumab Plus Bevacizumab.

Background

Objective

Patients and methods

Results

Conclusions

Publications

Adverse Events as Potential Predictive Factors of Activity in Patients with Advanced HCC Treated with Atezolizumab Plus Bevacizumab.

Similar Datasets

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