Safety Of Atezolizumab Research Articles

Is atezolizumab plus bevacizumab as first-line therapy for unresectable hepatocellular carcinoma superior to lenvatinib? a systematic review and meta‑analysis.

This meta-analysis was dedicated to evaluating the effectiveness and safety of Atezolizumab plus Bevacizumab (Atez/Bev) and Lenvatinib (LEN) as first-line systematic therapy for unresectable hepatocellular carcinoma (u-HCC). The prospective protocol for this study was registered with the PROSPERO (Registration number: CRD42022356874). Literature searches were conducted in PubMed, EMBASE database Cochrane Library, and Web Science to determine all clinical controlled studies that reported Atez/Bev and LEN for treating u-HCC. We. evaluated as primary end-point overall survival (OS) and progression-free survival (PFS), as well as other outcomes such as tumor response and adverse events (AEs).Quality assessment and data extraction of studies were conducted independently by three reviewers. Mean difference (MD) and odds ratio (OR) with 95% confidence interval (CI) were calculated using a fixed-effects or random-effects model. The meta-analysis was performed with RevMan 5.3 software. 12 retrospective cohort studies (RCSs) involving a total of 4948 patients were finally included. The results showed that compared with LEN, Atez/Bev can improve the patient's PFS (HR = 0.80, 95% CI: 0.72 ~ 0.88; p < 0.0001) and reduce the rate of overall AEs (OR = 0.46 95% CI: 0.38 ~ 0.55, p < 0.00001) and grade ≥ 3 AEs (OR = 0.43; 95% CI: 0.36 ~ 0.51, p < 0.00001), while there is no difference between OS and treatment responses rate (objective response rate, disease control rate, complete response, partial response, progressive disease, and stable disease) between two groups. In addition, the subgroup analysis shows that Atez/Bev can promote the OS of patients with viral hepatitis. (HR = 0.79, 95% CI: 0.67 ~ 0.95; p = 0.01), while LEN has an advantage in improving OS in patients with Child-Pugh grade B liver function (HR = 1.98, 95% CI: 1.50 ~ 2.63; p < 0.00001). Current evidence shows that compared with LEN, Atez/Bev has more advantages in PFS and safety in treating u-HCC and can improve the OS of patients with viral. LEN has advantages in improving the OS of patients with grade B liver function. However, more multicenter randomized controlled experiments are needed in the future to verify our results.

Outcomes and safety of atezolizumab plus bevacizumab in the treatment of hepatocellular carcinoma: treatment prognosis and comparison with tyrosine kinase inhibitors in a French multicenter matched real-life study.

The combination of atezolizumab plus bevacizumab (Atz/Bev) has radically changed the treatment strategy for advanced hepatocellular carcinoma (HCC) but raises questions. Our objectives were to determine survival outcomes and safety in a real-life multicenter French cohort, to investigate the on-treatment prognostic value of the bioinflammatory RECA score, and to perform a matched comparison with patients who previously received tyrosine kinase inhibitors (TKIs). A retrospective analysis of 109 consecutive patients enrolled from September 2020 to January 2023 and a post matched comparison with a TKI cohort ( n = 79) by the propensity score matching method. The Atz/Bev population was mainly nonviral disease patients (69%) with Child-Pugh grade A (90%), performance status 0/1 (90%), and Barcelona Clinic Liver Cancer stage B (38%) or stage C (62%) classification. After a median follow-up of 6.5 months (3.6-11.7), overall survival (OS) was 13.0 (5.1-28.7) months. OS was independently associated with metastasis, increased alkaline phosphatase, and serum bilirubin levels. Treatment-related adverse events were reported in 78% of patients, mostly grade 1 or 2. The RECA score clearly revealed two different prognosis groups after three cycles. No difference in OS was observed after matching between sequential treatment with TKIs and Atz/Bev. This real-life study highlights the importance of liver function when using Atz/Bev combination and the necessity of identifying predictive markers of response to HCC therapies. Our findings suggest a change in practices, with a marked proportion of intermediate stages, and support the on-treatment prognostic value of an inflammatory score.

Analysis of Factors Predicting the Real-World Efficacy of Atezolizumab and Bevacizumab in Patients with Advanced Hepatocellular Carcinoma.

Atezolizumab and bevacizumab have shown promising results for the treatment of advanced hepatocellular carcinoma (HCC) in clinical trials. In this study, the real-world efficacy and safety of atezolizumab and bevacizumab in treating advanced HCC were evaluated. In this retrospective study of patients at a Korean tertiary cancer center, 111 patients with Barcelona Clinic Liver Cancer stage B or C HCC received atezolizumab and bevacizumab as first-line therapy from May 2022 to June 2023. We assessed the progression-free survival (PFS), overall response rate (ORR), disease control rate (DCR), and adverse events. Patients with Barcelona Clinic Liver Cancer stage C HCC and Child-Pugh class A liver function were included in the study. The median PFS was 6.5 months, with an ORR of 27% and a DCR of 63%. Several factors, including the albumin-bilirubin grade, age, C-reactive protein and α-fetoprotein in immunotherapy score, macrovascular invasion, lung metastases, and combined radiotherapy, were found to significantly influence PFS (p<0.05). Patients with peritoneal seeding showed an higher ORR. The safety profile was consistent with that observed in clinical trials. Atezolizumab and bevacizumab demonstrated real-world efficacy in the treatment of advanced HCC, with ORRs and DCRs aligning with those observed in clinical trials. Variations in PFS and ORR based on specific risk factors highlight the potential of atezolizumab and bevacizumab in precision medicine for advanced HCC.

Comparison of Real-world Efficacy and Safety of Atezolizumab and Durvalumab in Combination With Chemotherapy for First-line Treatment of Extensive-stage Small-cell Lung Cancer.

The combination of programmed cell death ligand 1 inhibitors and platinum-based chemotherapy has become the standard treatment for first-line therapy in extensive-stage small-cell lung cancer (ES-SCLC). This study compared the efficacy and safety of atezolizumab plus chemotherapy and durvalumab plus chemotherapy in the treatment of ES-SCLC in clinical practice. We retrospectively analyzed 40 patients with ES-SCLC treated with atezolizumab plus chemotherapy or durvalumab plus platinum-based chemotherapy at the Fukuoka University Hospital between October 2019 and November 2022. Among the 40 patients, 20 were treated with atezolizumab and 20 were treated with durvalumab. There was no significant difference in patient characteristics between the two groups; five patients who received atezolizumab and one who received durvalumab showed a performance status of 2 or higher. The median progression-free survival of patients who received atezolizumab or durvalumab was 5.6 and 5.4 months, respectively (p=0.881). The median overall survival of patients who received atezolizumab or durvalumab was 10.0 and 17.1 months, respectively (p=0.163). The objective response rate of the patients who received atezolizumab or durvalumab was 80.0% and 85.0%, respectively. There was no significant difference in the incidence of immune-related adverse events between the groups. This retrospective study was the first to compare the efficacy and safety of PD-L1 antibody, atezolizumab or durvalumab, in combination with carboplatin and etoposide in treatment-naïve ES-SCLC Japanese patients in a real-world setting. Both regimens, atezolizumab or durvalumab with carboplatin and etoposide, were effective and well-tolerated in Japanese ES-SCLC patients, in line with clinical trial findings.

Efficacy and Safety of Atezolizumab plus Bevacizumab versus Sorafenib in Hepatocellular Carcinoma with Main Trunk and/or Contralateral Portal Vein Invasion in IMbrave150

Efficacy and Safety of Atezolizumab plus Bevacizumab versus Sorafenib in Hepatocellular Carcinoma with Main Trunk and/or Contralateral Portal Vein Invasion in IMbrave150

Efficacy and Safety of Atezolizumab as a PD-L1 Inhibitor in the Treatment of Cervical Cancer: A Systematic Review.

The efficacy and safety of PD-L1 inhibitors in the treatment of cervical cancer is an ongoing research question. This review aims to establish a clear profile of atezolizumab, examining its impact on survival outcomes, response rates, and safety measured by serious adverse events (SAEs). A literature search was conducted using PubMed, Scopus, and Web of Science, focusing on articles published up to February 2024. The review followed the PRISMA guidelines and synthesized outcomes from four randomized trial studies involving atezolizumab administered at 1200 mg IV every three weeks, alone or in combination with chemoradiotherapy. A total of 284 patients received atezolizumab, the majority being advanced stage cervical cancer (IVA-IVB). Median follow-up times ranged from 9 weeks to 32.9 months. It was found that combining atezolizumab with standard therapies extended median progression-free survival (PFS) from 10.4 to 13.7 months and overall survival (OS) from 22.8 to 32.1 months, according to the phase III trial. Monotherapy and initial treatment settings with atezolizumab also showed promising efficacy, with disease-free survival rates at 24 months reaching 79% compared to 52% with standard therapy alone. However, the treatment was associated with high rates of SAEs, reaching up to 79% in more intensive treatment combinations. Atezolizumab demonstrates significant potential in improving PFS and OS in patients with cervical cancer, supporting its inclusion as a first-line treatment option. Despite the efficacy benefits, the high incidence of SAEs necessitates careful patient selection and management strategies to mitigate risks. This systematic review supports the continued evaluation of atezolizumab in broader clinical trials to refine its therapeutic profile and safety measures in the context of cervical cancer treatment.

Atezolizumab in patients (pts) with tumor mutational burden (TMB)–high tumors from the TAPISTRY trial.

LBA2509 Background: Studies have suggested that pts with TMB-high tumors could derive clinical benefit from atezolizumab, a PD-L1 inhibitor; however, these studies used inconsistent TMB cutoffs. We report efficacy and safety data of atezolizumab in adult and pediatric pts with TMB-high advanced/metastatic solid tumors from Cohort D of the TAPISTRY trial (NCT04589845), using two TMB cutoffs: ≥13 mutations [mut]/Mb and ≥16 mut/Mb. Methods: TAPISTRY is a phase II, global, open-label, multicohort basket trial evaluating the efficacy and safety of multiple therapies in pretreated pts with advanced/metastatic solid tumors. Pts in Cohort D had advanced unresectable/metastatic, PD-L1 inhibitor-naïve, TMB-high (≥13 mut/Mb) solid tumors. Atezolizumab was given every 21 days, at 1200 mg in pts ≥18 years old, and at ≥15 mg/kg (up to 1200 mg) in pts &lt;18 years old. Tumor responses were assessed per RECIST v1.1. Primary endpoint: objective response rate (ORR) by independent review committee (IRC) in pts with TMB ≥16 mut/Mb. Secondary endpoints included ORR by IRC in pts with TMB ≥13 mut/Mb, duration of response (DoR), progression-free survival (PFS), overall survival (OS) and safety. Results: At data cut-off (Nov 9, 2023), 150 pts with TMB ≥13 mut/Mb were enrolled. In the safety-evaluable population (n = 148), median age was 63 years (range 11–86); 56% of pts were male, and 56% had received ≥2 prior lines of therapy (median 2; range 0–14). The efficacy-evaluable population included 129 pts with TMB ≥13 mut/Mb (TMB ≥16 mut/Mb; n = 111); the most common tumor types were colorectal (n = 40; 31%), breast, and gastroesophageal cancer (n = 11 each; 9%). Key outcomes are presented (Table). After a median follow-up of 9.8 months, ORR by IRC was comparable between pts with TMB ≥16 mut/Mb (22.5%) and pts with TMB ≥13 mut/Mb (20.2%). Responses were seen across a variety of tumor types. DoR 6- and 12-month event-free rates were 79% and 72%, respectively. Median PFS was short, suggesting fast disease progression in non-responders. Fatigue (22%) and anemia (20%) were the most common adverse events. Safety of atezolizumab was consistent with its known profile. Conclusions: Atezolizumab was well tolerated and led to antitumor activity in pts with TMB-high solid tumors. Responses were seen across a variety of tumor types. Clinical trial information: NCT04589845 . [Table: see text]

Efficacy and safety of second-line immunotherapy in patients with advanced non-small cell lung cancer.

e20571 Background: Patients (Pts) with advanced non-small cell lung cancer (NSCLC) face limited treatment options. Immunotherapy (IO) has revolutionized the treatment of NSCLC in this setting. The objective of our study is to evaluate the efficacy and safety of atezolizumab (Az) in Pts with advanced NSCLC in the second-line setting following progression on platinum-based chemotherapy (CT) in the Huelva area. Additionally, we aim to compare the results with those obtained in the phase 2 POPLAR and phase 3 OAK clinical trials. Methods: This is a descriptive and observational study conducted on patients with advanced NSCLC who received second-line IO with atezolizumab 1200 mg/1680 mg every 3 or 4 weeks, from 2015 to 2023 in the Huelva area (Spain). SPSS Statistics 22 was used for data analysis. Results: 26 Pts were treated, median age 67 years and 88.5% men. ECOG PS 0-1 in 92.3%. According to smoking habits, 42.3% were ex-smokers and 38.5% were active smokers. Regarding histology, 53.8% were non-squamous. 73.1% were inicial stage IV and 23% were stage III. Depending on the expression of PDL-1, PDL-1 was &lt; 1% in 34.6% (9 Pts) of the sample, between 1-49% in 53.8% (14 Pt) and unknown in 3 Pts. 26.9% of patients achieved disease stability and 11.5% achieved partial response. The response has not been evaluated in 38.5% because these patients maintain treatment. The adverse effects (AE) suffered by patients treated with Az in the second line were 53.8% grade (G) 1- 2 and 7.7% G 3-4. The most frequent were asthenia (48%), pruritus and arthralgia in 15.4%, both cases, and skin toxicity in 11.5%. In the case of the 2 Pts with G 3-4 toxicity, they were due to autoimmune anemia and asthenia with subsequent to grade 1, so treatment did not have to be interrupted. The median progression-free survival (PFS) was 2.7 months (m) (95% CI 0-6.8) and the median overall survival (OS) was 5.2 m (95% CI 0.5- 9-9). In both cases the results were not statistically significant. According to PDL1, no statistically significant differences were found in the subgroup analysis. Conclusions: Based on our results and those of the Phase 2 POPLAR and Phase 3 OAK studies, we consider that Az has an acceptable safety profile, with fewer G 3-4 side effects compared to CT, so a lower percentage of Pts drop out the treatment. Although the PFS was similar to the phase II-III studies, the OS was lower, probably due to the percentage of Pts with rapid progression and patients currently continuing to receive treatment, being a limitation in our study along with the small sample size. Despite this, our results are encouraging regarding the benefit of IO in Pts. Therefore, we conclude that the use of IO in these Pts falls within good clinical practice, offering them a clearly effective therapy and thus avoiding treatments with greater toxicity such as CT.

The safety of atezolizumab plus bevacizumab (atezo/bev) treatment in Chinese patients (pts) with hepatocellular carcinoma (HCC) with active hepatitis B virus (HBV) infection: Results from the TALENTop study.

e16168 Background: HCC pts with active HBV infection were excluded from most clinical trials involving immune checkpoint inhibitors because of safety concerns. We are aiming to evaluate the treatment safety of atezo/bev treatment in the TALENTop study (NCT04649489) which enrolled a large number of pts with active HBV infection. Methods: The TALENTop study is to clarify whether liver resection may provide additional benefits in Chinese HCC pts with macrovascular invasion who responded to conversion therapy with atezo/bev. After two versions of protocol modification, pts with active HBV infection were allowed. This study is ongoing, and the primary analysis is expected later. The current analysis is to evaluate treatment safety in pts with active HBV infection in the induction phase when pts received 3 cycles of atezo/bev and 1 cycle of atezo monotherapy. We compared the adverse events (AEs) between pts with active (baseline serum HBV-DNA ≥500 IU/mL) or inactive HBV infection (HBV-DNA &lt; 500 IU/mL). All pts with detectable HBV-DNA or positive hepatitis B surface antigen received oral antiviral therapy throughout the study. Results: From Apr 2021 to Sep 2023, 296 pts were enrolled and completed induction phase therapy of atezo/bev. 274 pts (92.6%) had HBV-related HCC, and 133 pts (44.9%) had active HBV infection. The baseline characteristics were mainly balanced between groups, except pts with active HBV infection were younger (52 vs 56 years, P = 0.024), had larger tumor size (the diameter of target lesion 88.3 vs 78.1 mm, P = 0.007), and had higher album-bilirubin score (-2.62 vs -2.80, P &lt; 0.001). In the induction phase, the AEs of any grade were higher in pts with active HBV infection (88.0% vs 73.6%, P = 0.002). However, the grade ≥3 AEs (20.3% vs 17.8%, P = 0.584), grade ≥3 treatment-related AEs (12.0% vs 12.3%, P = 0.950) and serious AEs (15.0% vs 13.5%, P = 0.706) were comparable between pts with active and inactive HBV infection. Additionally, the incidence of liver-related AEs was also comparable, including increased AST (17.3% vs 16.0%), increased ALT (17.3% vs 14.7%), and increased bilirubin (10.5% vs 12.9%). AEs leading to treatment withdrawal were also comparable (6.0% vs 6.1%, P = 0.966). In pts with active HBV infection, 20.8% remained serum HBV-DNA ≥500 IU/mL at the end of cycle 4. Conclusions: Active HBV infection did not compromise the safety of atezo/bev therapy. These findings could support that, with concurrent use of oral antiviral therapy, pts with active HBV infection should be not excluded from clinical trials or delayed for immunotherapy. Clinical trial information: NCT04649489 .

Efficacy and Safety of Atezolizumab and Bevacizumab in Appendiceal Adenocarcinoma.

Appendiceal adenocarcinoma (AA) remains an orphan disease with limited treatment options for patients unable to undergo surgical resection. Evidence supporting the efficacy of combined VEGF and PD-1 inhibition in other tumor types provided a compelling rationale for investigating this combination in AA, where immune checkpoint inhibitors have not been explored previously. We conducted a prospective, single-arm phase II study evaluating efficacy and safety of atezolizumab in conjunction with bevacizumab (Atezo+Bev) in advanced, unresectable AA. Patients treated with the Atezo+Bev combination had 100% disease control rate (1 partial response, 15 stable disease) with progression-free survival (PFS) of 18.3 months and overall survival not-yet-reached with median duration of follow-up of 40 months. These survival intervals were significantly longer relative to a clinically and molecularly matched synthetic control cohort treated with cytotoxic chemotherapy designed for colorectal cancer (PFS of 4.4 months, P = 0.041). In light of recent data demonstrating a lack of efficacy of 5-fluorouracil-based chemotherapy, Atezo+Bev is a promising treatment option for patients with low-grade unresectable AA; further study is warranted. AA remains an orphan disease with limited systemic therapy options for patients who are not candidates for surgical resection. These data suggest activity from combined VEGF and PD-L1 inhibition that warrants further study.

Real-World Pharmacokinetics, Effectiveness, and Safety of Atezolizumab in Patients With Unresectable Advanced or Recurrent NSCLC: An Exploratory Study of J-TAIL

IntroductionThis study validated real-world pharmacokinetic (PK) data using an established population PK (PopPK) model for atezolizumab in Japanese patients with NSCLC and explored the relationship between PK parameters, effectiveness, and adverse events (AEs) for the 1200 mg once every three weeks regimen. MethodsA subgroup of 262 of 1039 patients from J-TAIL consented to this exploratory research for PK evaluation of atezolizumab monotherapy for unresectable advanced/recurrent NSCLC (August 2018 to October 2019; 197 institutions). We evaluated plasma concentrations before the start of the third cycle of atezolizumab infusion classified into quartiles 1 to 4, their association with effectiveness, and the association between atezolizumab maximum plasma concentrations (Cmax) calculated using the existing PopPK model and AEs of special interest (AESIs). ResultsOverall, 175 of 262 patients were included; baseline characteristics were similar to those of patients enrolled in J-TAIL (Eastern Cooperative Oncology Group performance status ≥ 2, 12.0%; age ≥ 75 y, 28.9%; atezolizumab as more than or equal to third-line treatment, 57.5%). Atezolizumab plasma concentrations were similar to previously reported data among Japanese/non-Japanese patients. The overall survival was significantly shorter in patients with lower atezolizumab plasma concentrations in Q1 versus Q2 to Q4, although progression-free survival remained the same. The PK data adequately fit the PopPK model, with the frequency of AESIs increasing as the calculated Cmax at cycle 1 increased. ConclusionsIn real-world Japanese patients with unresectable advanced/recurrent NSCLC, PKs were similar to previous reports. Certain patient populations had shorter overall survival, and atezolizumab plasma concentrations in cycle 3 were lower in this population. Elevated Cmax at cycle 1 may be associated with an increased frequency of AESIs.

Abstract CT235: RNA-seq molecular subtypes and gene expression signatures in the phase 3 IMpower151 study of 1L bevacizumab + pemetrexed/paclitaxel ± atezolizumab in metastatic NSCLC

Abstract Introduction IMpower151 (NCT04194203) was a phase 3 study to evaluate the efficacy and safety of atezolizumab, bevacizumab, carboplatin, plus paclitaxel or pemetrexed (ABCP) vs BCP, as 1L treatment for metastatic nsqNSCLC. IMpower151 did not meet its primary endpoint of INV-PFS. The objectives of this biomarker analysis were to characterize the molecular subtypes of metastatic nsqNSCLC and to explore the relationship between molecular subtype, predefined gene expression signatures, PD-L1 status and clinical outcomes with ABCP and BCP. Methods RNA sequencing of 250 nsqNSCLC tumor samples from IMpower151 was analyzed in the ACBP (n=123) and BCP (n=127) treatment arms. Non-negative matrix factorization (NMF) was applied to variably expressed genes to define molecular subtypes. Gene expression signatures were defined based on previously published associations with their respective biology. Tumor PD-L1 levels were determined by SP263 immunohistochemistry (Ventana). Results No PD-L1 dependent difference of survival benefit of ABCP compared to BCP was observed at the cutoff of TC 1% or TC 50%. Four molecular subtypes (NMF1-NMF4) were identified based on RNA sequencing. NMF1 (n=78) were immune-depleted and had low tumor proliferation. NMF2 (n=73) were characterized by low level of anti-tumor immune cells, increased expression of stromal signatures and high tumor proliferation. NMF3 (n=65) had the most inflamed transcriptomic profile with high enrichment of immune cells, and increased expression of stromal signatures as well. NMF4 (n=34) had the enrichment of granulocytes, a less inflamed immunophenotype and decreased expression of stromal signatures. The positive rate of PD-L1 expression with TC&amp;gt;=1% was significantly lower in NMF1 compared to other subtypes. None of patients with the four NMF subtypes showed significantly longer PFS or OS with ABCP than BCP. Overall, patients with NMF2 showed numerically shorter PFS and patients with NMF3 showed numerically longer PFS than other subtypes. Gene expression signatures of antitumor cytokines are correlated with survival benefit of ABCP compared to BCP. Patients with high expression level of antitumor cytokines showed substantially improved PFS and OS benefit from ABCP than BCP in both ITT population and EGFR mutation population. Conclusion Four molecular subtypes of nsqNSCLC with different immune-cell and tumor microenvironmental features were characterized. NMF2 may identify a fibrotic and immune-depleted subgroup correlated with worse prognosis. NMF3 may identify an immune-inflamed subgroup correlated with better prognosis. Neither NMF subtypes nor PD-L1 IHC level showed a correlation with survival benefit of ABCP controlled by BCP. The gene expression signature of antitumor cytokines could serve as a potential predictive biomarker for survival benefit of ABCP in metastatic nsqNSCLC including EGFR mutant patients. This finding is based on the exploratory analysis of a single clinical trial with limited sample size. It needs further investigation in other cohorts of tumor tissues and with larger clinical potential in blood samples as well. Citation Format: Caicun Zhou, Charlie Sun, Stacey Huang, Xiaorong Dong, Gongyan Chen, Zhehai Wang, Xianghua Wu, Yu Yao, Yiping Zhang, Ying Cheng, Hongming Pan, Xiaodong Zhang, Jiuwei Cui, Lifeng Wang, Xi Chen, Xiaoling Li, Ziping Wang, Qiming Wang, Jianxing He, Mengzhao Wang, Li Qian, Habib Hamidi, Shanshan Li, Marcus Ballinger, David S. Shames, Minu Srivastava. RNA-seq molecular subtypes and gene expression signatures in the phase 3 IMpower151 study of 1L bevacizumab + pemetrexed/paclitaxel ± atezolizumab in metastatic NSCLC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT235.

Abstract 5097: Effectiveness and safety of atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma: A multicenter, retrospective real-world study in China

Abstract Background: Atezolizumab plus bevacizumab (Atezo+Bev) has shown better benefits than sorafenib as the first-line treatment for unresectable hepatocellular carcinoma (uHCC) in IMbrave 150. However, the real-world evidence of Atezo+Bev in uHCC is limited, especially in China. We aimed to investigate the real-world effectiveness and safety of Atezo+Bev in Chinese patients with uHCC. Methods: Patients with uHCC treated with Atezo+Bev were included at 5 centers in China from Jan. 2021 to Jan. 2023. Overall response (ORR), organ-specific response rate (OSRR), disease control rates (DCR), time to disease progression (TPP), progression-free survival (PFS), metastasis-specific PFS and overall survival (OS) were calculated. Results: Among 48 patients, the median age was 58.4 years with 85.4% being male. A total of 35 and 13 patients received Atezo+Bev as 1st and 2nd line treatment, respectively. The median number of treatment cycles were 8, and 27 (56.3%) patients received locoregional therapies. Detailed treatment response is in the Table. The overall ORR and DCR assessed by mRECIST were 60.4% and 75.0%, while the intra- and extrahepatic OSRR were 59.4% and 62.5%, respectively. With a median follow-up of 14.5 months, the median PFS was 8.5 months (95%CI: 4.4, 11.2) in 1st line setting and 5.1 months (95%CI: 2.1, 7.9) in 2nd line setting. Median intra- and extrahepatic metastasis-specific PFS were 7.9 and 7.6 months, respectively. Median overall TTP was 7.6 months. The median OS was not reached. A total of 36 patients (75%) experienced any grade adverse events, most commonly being thrombocytopenia (27.1%, n=13), lymphopenia (25%, n=12) and abnormal liver function (14.6%, n=7). Conclusion: This study confirmed effectiveness and safety of Atezo+Bev in the 1st line treatment of uHCC, and observed its potential in 2nd line in a real-world setting. Further studies are warranted to confirm these observations and refine treatment strategies. Table. Treatment response N (%) Response Evaluation Criteria in Solid Tumors (RECIST) 1.1(N=48) Modified RECIST(N=48) Complete response (CR) 7 (14.6) 9 (18.8) Partial response (PR) 12 (25.0) 20 (41.7) Stable disease (SD) 15 (31.2) 7 (14.6) Progressive disease 11 (22.9) 12 (25.0) Not evaluated 3 (6.2) 0 ORR (CR+PR) 19 (39.6) 29 (60.4) DCR (CR+PR+SD) 34 (70.8) 36 (75.0) Citation Format: Hui Zhang, Minghua Shao, Binbin Tan, Yin Fu, Yuan, Hailei Chen. Effectiveness and safety of atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma: A multicenter, retrospective real-world study in China [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5097.

Efficacy and safety of atezolizumab plus bevacizumab in patients with portal hypertension for unresectable hepatocellular carcinoma.

Atezolizumab plus bevacizumab combination therapy (Atezo + Beva) is used as the first-line therapy for unresectable hepatocellular carcinoma (u-HCC). Serious adverse events (AEs), including rupture of esophagogastric varices, have been seen during treatment. Therefore, the relationships of efficacy, safety, and portal hypertension (PH) were analyzed. A total of 146 patients with u-HCC and Child-Pugh Scores of 5-7 received Atezo + Beva. Prophylactic treatment for varices was performed for patients with the risk of rupture of varices before the start of Atezo + Beva. A propensity score-matched cohort was created to minimize the risk of potential confounders. Efficacy was assessed in 41 propensity score-matched pairs. AEs were assessed between patients without PH (n = 80) and with PH (n = 66). In patients without PH and with PH, median overall survival was 18.4 months and 18.8 months (p = 0.71), and median progression-free survival was 8.6 months and 5.8 months (p = 0.92), respectively. On the best radiological response evaluation for Response Evaluation Criteria in Solid Tumors, the objective response rate was 31.7% and 26.8% (p = 0.81), respectively. Variceal rupture occurred in three patients with PH, but there were no significant differences in the occurrence of variceal rupture (p = 0.090) and Grade 3-4 AEs between patients without and with PH. No significant differences in efficacy and safety were observed with PH. Prophylactic treatment for varices before the start of Atezo + Beva would allow treatment to continue relatively safely.

Clinical outcomes of atezolizumab versus standard-of-care docetaxel with and without ramucirumab in patients with advanced non-small-cell lung cancer who received prior immunotherapy.

Atezolizumab is superior to docetaxel for patients with advanced non-small-cell lung cancer (NSCLC) who are pretreated with platinum-based chemotherapy based on the POPLAR and OAK trials. However, patients who received prior immunotherapy were excluded from these trials. The standard of care second-line therapy for these patients remains to be docetaxel with or without ramucirumab. The efficacy and safety of atezolizumab as a subsequent therapy in immunotherapy-pretreated patients are unknown. We conducted a retrospective study of all patients with locally advanced or metastatic NSCLC who were pretreated with immunotherapy at Mayo Clinic Jacksonville and Rochester from 2016 to 2022. Patients who received subsequent therapy of atezolizumab alone (Atezo), docetaxel (Doce), or docetaxel + ramucirumab (Doce+Ram) were included. In this cohort of 165 patients, 12.7% (n=21), 49.1% (n=81), and 38.2% (n=63) patients received subsequent Atezo, Doce, and Doce+Ram, respectively. 1-year landmark progression-free survival (PFS) were 23.8%, 6.2%, and 3.2% (p=0.006), and 2-year landmark PFS were 14.3%, 0%, and 0% (p<0.0001), in the Atezo, Doce, and Doce+Ram groups, respectively. About 20% patients with positive PD-L1 had durable response to atezolizumab. The Atezo group showed significantly greater overall survival (OS) improvement over Doce group (median OS 17.7 vs. 7.7 months, HR 0.47, 95% CI 0.29 - 0.76, p=0.008), and over Doce+Ram group (median OS 17.7 vs. 8.9 months, HR 0.55, 95% CI 0.32 - 0.95, p=0.047). 4 of 21 (19%) patients in the Atezo group developed immune-related adverse events (irAE). We observed statistically significant and clinically meaningful overall survival benefits of atezolizumab monotherapy compared with docetaxel +/- ramucirumab in patients with advanced NSCLC who were pretreated with immunotherapy. The survival benefit seems to be mainly from PD-L1 positive patients. Subsequent immunotherapy with Atezolizumab did not increase irAE rate.

Efficacy and safety of atezolizumab and bevacizumab in real-world treatment of advanced hepatocellular carcinoma: experience from a cancer center in Brazil

Efficacy and safety of atezolizumab and bevacizumab in real-world treatment of advanced hepatocellular carcinoma: experience from a cancer center in Brazil

Impact of Bevacizumab Being Skipped due to Adverse Events of Special Interest for Bevacizumab in Patients with Unresectable Hepatocellular Carcinoma Treated with Atezolizumab plus Bevacizumab: An Exploratory Analysis of the Phase III IMbrave150 Study

Introduction: The 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). Methods: Patients 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. Results: Of 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/Conclusion: Efficacy 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.

Atezolizumab addition to platinum doublet: evaluating survival outcomes for patients with extensive disease small cell lung cancer.

The efficacy of adding atezolizumab to the platinum doublet regimen for extensive disease small cell lung cancer (ED-SCLC) remains marginally limited. We retrospectively assessed the real-world efficacy and safety of atezolizumab in addition to carboplatin and etoposide (EP + A), versus carboplatin and etoposide (EP) alone in previously untreated ED-SCLC patients. From a total of 99 patients, 46 were assigned to the EP + A group, and 53 to the EP group. No significant difference was observed in progression-free survival between the groups. However, the overall survival (OS) was significantly longer in the EP + A group (20.8 vs 12.1months; HR: 0.52; p = 0.0127). Patients older than 70years, male, with performance status 0-1, without liver metastasis, and low levels of C-reactive protein and neutrophil-lymphocyte ratio, experienced longer OS in the EP + A group compared to the EP group. The addition of atezolizumab to the platinum doublet regimen significantly extended OS in ED-SCLC patients, particularly among certain subgroups, suggesting its potential value in personalized treatment strategies. Further investigation is warranted to validate these findings.

Effectiveness and safety of atezolizumab, nivolumab and pembrolizumab in metastatic non-small cell lung cancer

ObjectiveTo determine the effectiveness and safety of atezolizumab, nivolumab and pembrolizumab in patients with non-small cell lung cancer. MethodThis is a retrospective observational study including patients treated in second line and beyond. The effectiveness of treatment was assessed by means of overall survival and progression free survival measurements. Toxicity was described according to the Common Criteria for Adverse Event Terminology v5.0. ResultsThe study included 8 patients treated with atezolizumab,19 with nivolumab, and 16 with pembrolizumab. Median progression free survival with atezolizumab was 9.6 months (95%CI 2-17.2), 12.6 months (95%CI 6.9-18.2) for nivolumab, and 8.5 months (95%CI 0-19) for pembrolizumab. Median overall survival was 13.4 months (95%CI 6-20.9) for nivolumab. Both PFS and OS were statistically higher in patients with grade 0-1 metastasis in the case of nivolumab, and in ECOG 0-1 patients for pembrolizumab. Median overall survival was not reached for atezolizumab or pembrolizumab. Around 85% of patients suffered adverse effects of some degree. Two of the patients treated with nivolumab developed vitiligo. Overall survival of both was higher than 2.5 years. ConclusionsFor the patients included in the sample, nivolumab was less effective in those with two or more metastases; the effectiveness of pembrolizumab was lower in ECOG-2 patients. Vitiligo was related to a more durable response to treatment.

Efficacy and safety of atezolizumab plus bevacizumab versus lenvatinib for unresectable hepatocellular carcinoma: a systematic review and meta-analysis.

Atezolizumab plus bevacizumab and lenvatinib are the current first-line systematic therapy for unresectable hepatocellular carcinoma (uHCC). However, the selection of initial treatment among the two therapies are controversial. This meta-analysis aims to compare efficacy and safety between atezolizumab plus bevacizumab and lenvatinib. We systematically searched for studies on atezolizumab plus bevacizumab and lenvatinib in the online databases PubMed, Embase, Web of Science and Cochrane Library. The outcome data including overall survival (OS), progression free survival (PFS), tumor response and adverse events (AEs), were independently extracted by two authors in a standardized way. Eight retrospective cohort studies with 3690 patients (atezolizumab plus bevacizumab: 1680, lenvatinib: 2010) were included in the meta-analysis. The atezolizumab plus bevacizumab group had significant longer PFS [hazard ratio (HR) 0.76, 95% confidence intervals (CI) 0.65-0.88; I squared statistic (I2) = 0.0%, p = 0.590], compared with lenvatinib group but no significant difference in OS (HR 0.87, 95% CI 0.75-1.01; I2 = 0.0%, p = 0.597), objective response rate (ORR) [risk ratio (RR) 0.89, 95% CI 0.79-1.02; I2 = 19.3%, p = 0.283] and disease control rate (DCR) (RR 1.03, 95% CI 0.98-1.09; I2 = 0.0%, p = 0.467) among them. Moreover, patients receiving atezolizumab plus bevacizumab exhibited lower incidences of grade 3/4 AEs than those receiving lenvatinib (RR 0.65, 95% CI 0.51-0.83; I2 = 69.3%, p = 0.003). However, in non-viral patients group, lenvatinib delivered favorable outcomes in OS (HR 1.32, 95% CI 1.04-1.67; I2 = 0.0%, p = 0.380) compared with atezolizumab plus bevacizumab. Atezolizumab plus bevacizumab provides potential advantage in efficacy and better safety than lenvatinib in the treatment of uHCC. Lenvatinib is an appropriate effective alternative to atezolizumab plus bevacizumab in patients without viral infecting.