Different organ-specific response to nivolumab to determine the survival outcome of patients with advanced hepatocellular carcinoma (aHCC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4584-4584
Author(s):  
Han Sang Kim ◽  
Jung Yong Hong ◽  
Jaekyung Cheon ◽  
Ilhwan Kim ◽  
Chang Gon Kim ◽  
...  
Keyword(s):  
Lymph Node ◽  
Liver Function ◽  
Tumor Burden ◽  
Phase Iii ◽  
Survival Outcomes ◽  
Specific Response ◽  
Advanced Hepatocellular Carcinoma ◽  
Clinicopathological Factors ◽  
Organ Specific ◽  
Intrahepatic Tumor

4584 Background: Previously, two phase III clinical trials of immune checkpoint inhibitors (ICI) failed to meet their primary endpoints, leading to doubts regarding the clinical activity of ICI monotherapy in patients with aHCC. Here, we comprehensively examined clinicopathological factors and estimated their association with survival outcomes in aHCC patients treated with nivolumab. Methods: A total of 261 eligible patients from 5 high-volume centers who were treated with nivolumab between June 9, 2012 and March 14, 2018 and had measurable diseases were reviewed. We reviewed more than 80 clinicopathological factors and categorized them into 6 areas: 1) demographics (n = 16); 2) baseline laboratory values (n = 19); 3) tumor burden (n = 12); 4) previous treatment (n = 12); 5) treatment response (n = 5); 6) toxicity profiles (n = 18). Their association with survival outcomes were evaluated, and organ-specific response evaluation, adapted from RECIST 1.1, was conducted. Results: Of the 261 patients, 218 (84%) had extrahepatic spread. The median follow-up time was 4.5 months. The median progression-free survival (PFS) and overall survival (OS) were 2.3 months (95% CI, 1.8-2.8) and 6.3 months (95% CI, 5.0-8.2). Objective response rate was 15%. Subgroup analyses revealed that compensated liver function (Child-Pugh score A5/6), surrogate markers for low tumor burden (low AFP, low PIVKA, and low LDH level), inflammatory markers (low C-reactive protein [CRP], low erythrocyte sedimentation rate [ESR], low neutrophil-to-lymphocyte ratio [NLR], high lymphocyte-to-monocyte ratio [LMR]), and low intrahepatic tumor burden were significantly associated with longer OS. A total of 456 individual lesions (liver, n = 249; lung, n = 124; lymph node, n = 35; others such as boner soft tissues, n = 48) were examined. Organ-specific response rates (hepatic tumor, 9%; lung, 25%; lymph node, 37%; others metastasis, 15%) were different, of which intrahepatic tumor was the least responsive organ to ICI treatment in aHCC. Conclusions: Underlying liver function, the tumor extent and burden, and the degree of plasma lymphocytes are crucial for determining tumor response to ICI in aHCC. Antitumor immune response to ICI differs in an organ-specific manner. The hepatic tumors of HCC may be less responsive to nivolumab than extrahepatic lesions.

Survival of SLNB-positive melanoma patients with and without complete lymph node dissection: A multicenter, randomized DECOG trial.

2015 ◽  
Vol 33 (18_suppl) ◽  
pp. LBA9002-LBA9002 ◽  
Author(s):  
Ulrike Leiter ◽  
Rudolf Stadler ◽  
Cornelia Mauch ◽  
Werner Hohenberger ◽  
Norbert Brockmeyer ◽  
...  
Keyword(s):  
Lymph Node ◽  
Lymph Node Dissection ◽  
Distant Metastases ◽  
Tumor Burden ◽  
Phase Iii ◽  
Node Dissection ◽  
Significant Treatment ◽  
Melanoma Patients ◽  
Complete Lymph Node Dissection

LBA9002 Background: Complete lymph node dissection (CLND) following positive sentinel node biopsy (SLNB) was evaluated in a randomized phase III trial. Methods: 1,258 patients with cutaneous melanoma of the trunk and extremities and with positive SLNB were evaluated. Of these, 483 (39%) agreed to randomization into the clinical trial. 241 patients underwent observation only, 242 received CLND. Both groups had a subsequent 3-years follow-up. Recurrence-free (RFS), distant metastases free (DMFS) and melanoma specific (MSS) survival were analyzed as endpoints. Results: Patient enrolment was performedfrom January 2006 to December 2014. In the intent to treat analysis, both groups did not differ significantly in distribution of age, gender, localization, ulceration, tumor thickness (median 2,4 mm in both groups), number of positive nodes, or tumor burden in the SN. The mean follow-up time was 34 months (SD ± 22.1). No significant treatment-related difference was seen in the 5-years RFS (P = 0.72), DMFS (P= 0 .76) and MSS (P = 0.86) in the overall study population. Conclusions: In this early analysis of trial results, no survival benefit was achieved by CLND in melanoma patients with positive SLNB. A subsequent analysis three years after inclusion of the last patient is planned.

scholarly journals Organ Specific Responses to First-line Lenvatinib Plus Anti-PD-1 Antibodies in Patients With Unresectable Hepatocellular Carcinoma: a Retrospective Analysis

2021 ◽  
Author(s):  
Cheng Huang ◽  
Xiao-Dong Zhu ◽  
Ying-Hao Shen ◽  
Dong Wu ◽  
Yuan Ji ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Retrospective Analysis ◽  
Surgical Resection ◽  
Chinese Patients ◽  
Specific Response ◽  
Advanced Hepatocellular Carcinoma ◽  
First Line ◽  
Advanced Hcc ◽  
Overall Response ◽  
Organ Specific

Abstract BackgroundWe evaluated organ-specific response rates (OSRRs) to first-line lenvatinib plus anti-PD-1 antibodies in patients with advanced hepatocellular carcinoma (HCC).MethodsThis retrospective analysis included Chinese patients with unresectable/advanced HCC who received first-line lenvatinib (8 mg/day) plus ≥3 infusions of anti-PD-1 antibodies between October 2018 and May 2020. Tumor and macrovascular tumor thrombi (MVTT) treatment responses were evaluated every 2 months using RECIST v1.1. The overall response rate (ORR)/OSRR was defined as the percentage of patients with a best overall response of complete or partial response (CR or PR).ResultsIn total, 60 patients were included in the analysis; 96.7% had measurable intrahepatic lesions, 55% had MVTT and 26.7% had extrahepatic disease. In all 60 patients, the ORR was 33.3%, median progression-free survival was 7.0 months (95% CI, 1.7-12.3) and median overall survival was not reached. The OSRR for MVTT (54.5%) was higher versus intrahepatic tumors (32.8%), extrahepatic lung metastases (37.5%) and lymph node metastases (33.3%). Among 33 patients with intrahepatic tumors and MVTT, 18 had differential responses in each site, including 13 with a better response in MVTT versus intrahepatic lesions. Among 18 patients whose MVTT achieved a radiographic CR or PR, six underwent surgical resection: 4/6 achieved a pathological CR in MVTT and 2/6 in the intrahepatic tumor.ConclusionsFirst-line lenvatinib plus anti-PD-1 antibodies resulted in better tumor responses in MVTT versus intrahepatic lesions. Complete MVTT necrosis may allow downstaging and subsequent eligibility for surgical resection in a proportion of patients with advanced HCC.

Hepatic arterial infusion chemotherapy of oxaliplatin plus fluorouracil versus sorafenib in advanced hepatocellular carcinoma: A biomolecular exploratory, randomized, phase 3 trial (The FOHAIC-1 study).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4007-4007
Author(s):  
Ning Lyu ◽  
Ming Zhao
Keyword(s):  
Median Overall Survival ◽  
Hepatic Arterial Infusion ◽  
Tumor Burden ◽  
Advanced Hepatocellular Carcinoma ◽  
Arterial Infusion ◽  
Phase 3 ◽  
Infusion Chemotherapy ◽  
Extrahepatic Metastases ◽  
To Receive ◽  
Intrahepatic Tumor

4007 Background: Advanced hepatocellular carcinoma (HCC) with mega liver masses and macrovascular invasion were commonly observed at the first diagnosis, while with less extrahepatic metastases (77.5% vs. 37.9%). However, in clinical trials IMbrave150, SHARP, and Asia-Pacific SHARP, the percentage of extrahepatic metastases reached 63%, 53%, and 68.7%, respectively, while macrovascular invasion only accounted for 38%, 36%, and 36%. Unlike the previous and ongoing phase 3 clinical trials exploring the optimal systemic medication in the first-line treatment of advanced HCC, this study mainly focused on a population with a heavy intrahepatic tumor burden. Methods: In this open-label, phase 3 trial, patients were randomly assigned in a 1:1 ratio to undergo hepatic arterial infusion chemotherapy (HAIC) of FOLFOX regimens (HAIC-FO) or sorafenib treatment. Patients in the HAIC-FO group were recommended to receive tumor and normal tissue biopsy to search for the potential genomic biomarkers in predicting the response to treatment. Results: Between May 2017 and May 2020, 551 patients were recruited. Two hundred sixty eligible patients were randomly assigned to receive HAIC-FO (n = 130) or sorafenib (n = 132) and were included in the intention-to-treatment population. Macrovascular invasion with or without extrahepatic metastasis was present in 82.8% of patients (84.6% and 81.1%; P = 0.446). The median tumor diameter was 11.7 cm (IQR 8.3-14.0) of the HAIC-FO group and 10.8 cm (8.7-13.6) of the sorafenib group (P = 0.439). The percentage of patients with > 50% tumor volume involvement of the liver was 41.5% and 39.4%, respectively (P = 0.724). At the time of data cutoff (Oct 31, 2020, at 190 deaths [79 of HAIC-FO and 111 of sorafenib]), patients receiving HAIC-FO had a median overall survival of 13.9 months (95%CI 10.6-17.2), compared with 8.2 months (7.5-9.0) for those receiving sorafenib (HR 0.408 [95%CI 0.301-0.552], P < 0.001). Tumor downstaging occurred in 16 (12.3% of 130) patients of the HAIC-FO group, including 15 (93.8%) receiving curative surgery or ablation and finally achieving a median overall survival (progression-free survival) of 20.8 (16.4) months (95%CI 9.1-32.5 [7.5-25.3]) with a 1-year rate of 93.8% (68.8%). Analyses of predictive biomarkers based on the whole genome sequencing were ongoing in the HAIC-FO group. Conclusions: This randomized phase 3 study proved that HAIC-FO had superior efficacy and survival outcome than sorafenib in the first-line treatment of primary diagnostic, advanced HCC, indicating that patients with heavy intrahepatic tumor burden, HAIC-FO monotherapy might be a better strategy than sorafenib. Clinical trial information: NCT03164382.

Radiomic signatures to predict survival in patients with advanced hepatocellular carcinoma (HCC) treated with sorafenib +/- doxorubicin: Correlative science from CALGB 80802 (Alliance).

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 343-343
Author(s):  
Laurent Dercle ◽  
Susan Michelle Geyer ◽  
Andrew B. Nixon ◽  
Federico Innocenti ◽  
Qian Shi ◽  
...  
Keyword(s):  
Error Rate ◽  
Tumor Volume ◽  
Quantitative Imaging ◽  
Measurement Techniques ◽  
Tumor Burden ◽  
Phase Iii ◽  
Advanced Hepatocellular Carcinoma ◽  
Imaging Features ◽  
Time Points ◽  
Validation Set

343 Background: Alliance/CALGB 80802, a randomized phase III trial, evaluated sorafenib plus doxorubicin vs. doxorubicin in pts with HCC and showed no improvement in median overall survival (OS) (HR[95CI] 1.05[0.83-1.31]) or PFS (HR[95CI] 0.93[0.75-1.16]). In HCC surrogacy of tumor response with OS remains controversial, in part due to varying criteria used for response evaluation (e.g., RECIST1.1 and mRECIST). We evaluated the performance of several models to predict OS using pretreatment clinical and radiomic variables. Methods: In CALBG 80802, we segmented all measurable tumor lesions on sequential CT scans. A lesion’s imaging phenotype was deciphered with 23 uncorrelated quantitative imaging features measured at baseline and week (wk) 10 (first follow-up). An OS landmark survival analysis was conducted at wk 10. Patients were randomly assigned (3:1) to training (n = 92) and validation (n = 37) sets. In a training set, 6 random forest predictive models (6 signatures) used features that best predicted OS using 3 sets of variables: radiomics only (n = 23), clinical only (n = 9), radiomics and clinical (n = 32). Two time points (baseline only or baseline + wk 10) were assessed. Each signature's output was an individualized prediction and a continuous value ranging from 0 to 1 (from most to least favorable predicted OS). The primary endpoint was to compare these models' performance to predict OS using error rate (Harrell's concordance-index) in the validation set. Results: Of the 6 training signatures evaluated, the one achieving the highest performance in the validation set was an 8-feature signature combining radiomics and clinical variables measured at two time points (baseline + wk 10) with an error rate of 35.6%. The variables [rank of importance] (table) selected by the signature included baseline clinical features (albumin[1], AFP[2], Child-Pugh[4]), baseline radiomics features (component 17[3], component 1[5], component 9[7], tumor volume[8]) and wk 10 radiomics features (delta tumor volume[6]). Variable delta tumor volume [6] used a more enhanced estimation of tumor burden at baseline and a delta tumor volumetric measurement; compared to RECIST1.1 measurement of percentage change in unidimensional measurement of a subset of target lesions. The four quartiles of the signature were significantly associated with OS (Log-Rank, P < 0.0001). Conclusions: The selected combined radiomic and clinical composite signature provided the best prediction for OS in the 80802 study patients’ population. It is a suggested way forward to go beyond single anatomic measurement techniques such as RECIST or mRECIST. [Table: see text]

scholarly journals Organ specific responses to first-line lenvatinib plus anti-PD-1 antibodies in patients with unresectable hepatocellular carcinoma: a retrospective analysis

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Cheng Huang ◽  
Xiao-Dong Zhu ◽  
Ying-Hao Shen ◽  
Dong Wu ◽  
Yuan Ji ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Retrospective Analysis ◽  
Surgical Resection ◽  
Chinese Patients ◽  
Specific Response ◽  
Advanced Hepatocellular Carcinoma ◽  
First Line ◽  
Advanced Hcc ◽  
Overall Response ◽  
Organ Specific

Abstract Background We evaluated organ-specific response rates (OSRRs) to first-line lenvatinib plus anti-PD-1 antibodies in patients with advanced hepatocellular carcinoma (HCC). Methods This retrospective analysis included Chinese patients with unresectable/advanced HCC who received first-line lenvatinib (8 mg/day) plus ≥3 infusions of anti-PD-1 antibodies between October 2018 and May 2020. Tumor and macrovascular tumor thrombi (MVTT) treatment responses were evaluated every 2 months using RECIST v1.1. The overall response rate (ORR)/OSRR was defined as the percentage of patients with a best overall response of complete or partial response (CR or PR). Results In total, 60 patients were included in the analysis; 96.7% had measurable intrahepatic lesions, 55% had MVTT and 26.7% had extrahepatic disease. In all 60 patients, the ORR was 33.3%, median progression-free survival was 7.0 months (95% CI, 1.7–12.3) and median overall survival was not reached. The OSRR for MVTT (54.5%) was higher versus intrahepatic tumors (32.8%), extrahepatic lung metastases (37.5%) and lymph node metastases (33.3%). Among 33 patients with intrahepatic tumors and MVTT, 18 had differential responses in each site, including 13 with a better response in MVTT versus intrahepatic lesions. Among 18 patients whose MVTT achieved a radiographic CR or PR, six underwent surgical resection: 4/6 achieved a pathological CR in MVTT and 2/6 in the intrahepatic tumor. Conclusions First-line lenvatinib plus anti-PD-1 antibodies resulted in better tumor responses in MVTT versus intrahepatic lesions. Complete MVTT necrosis may allow downstaging and subsequent eligibility for surgical resection in a proportion of patients with advanced HCC.

Association of adverse events (AEs) with efficacy outcomes for cabozantinib (C) in patients (pts) with advanced hepatocellular carcinoma (aHCC) in the phase III CELESTIAL trial.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4088-4088 ◽  
Author(s):  
Ghassan K. Abou-Alfa ◽  
Tim Meyer ◽  
Ann-Lii Cheng ◽  
Irfan Cicin ◽  
Luigi Bolondi ◽  
...  
Keyword(s):  
Liver Function ◽  
Kinase Inhibitors ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Advanced Hepatocellular Carcinoma ◽  
Previously Treated ◽  
Baseline Characteristics ◽  
Grade 3 ◽  
Ecog Ps ◽  
Tumor Types

4088 Background: Class-specific AEs occurring with tyrosine kinase inhibitors have been associated with improved efficacy outcomes in several tumor types including aHCC. In the phase 3 CELESTIAL trial (NCT01908426), C, an inhibitor of VEGFR, MET, and AXL, improved overall survival (OS) and progression-free survival (PFS) vs placebo (P) in pts with previously treated aHCC. Here, we retrospectively evaluate the association of palmar-plantar erythrodysaesthesia (PPE) and hypertension (HTN) with OS and PFS for C in the CELESTIAL trial. Methods: 707 pts with aHCC were randomized 2:1 to receive 60 mg C or P once daily. Eligible pts had Child-Pugh score A, ECOG PS ≤1, must have received prior sorafenib, and could have received up to two prior regimens of systemic therapy for HCC. OS and PFS with C were evaluated for pts with any grade PPE or grade ≥3 HTN within the first 8 weeks of study treatment. Results: Overall, 374 (80%) pts in the C arm and 179 (76%) pts in the P arm completed ≥8 weeks of treatment. In the first 8 weeks, 188 (40%) of C-treated pts developed any grade PPE vs 11 (5%) of P-treated pts, and 61 (13%) of C-treated pts developed grade ≥3 HTN vs 3 (1%) of P-treated pts. Median OS with C was 14.4 mo for pts with any grade PPE vs 8.4 mo for pts without PPE (HR 0.59, 95% CI 0.47-0.74), and median PFS with C was 6.5 mo vs 3.7 mo, respectively (HR 0.63, 95% CI 0.51-0.78). Median OS with C was 16.1 mo for pts with grade ≥3 HTN vs 9.5 mo for pts without grade ≥3 HTN (HR 0.56, 95% CI 0.39-0.80), and median PFS with C was 7.4 mo vs 4.4 mo, respectively (HR 0.59, 95% CI 0.43-0.82). Some imbalances in baseline characteristics were present. Pts with PPE had better ECOG PS (60% vs 47% ECOG 0), better liver function (48% vs 34% ALBI grade 1), and less macrovascular invasion (24% vs 30%) than those without. Likewise, pts with grade ≥3 HTN had better ECOG PS (61% vs 51% ECOG 0), better liver function (56% vs 37% ALBI grade 1), and less macrovascular invasion (20% vs 29%) than those without. Conclusions: The development of PPE or grade ≥3 HTN with C was associated with prolonged OS and PFS in pts with previously treated aHCC although some imbalances in baseline characteristics between comparator groups were present. Clinical trial information: NCT01908426.

Real-world efficacy and safety of lenvatinib-base therapy for patients with unresectable hepatocellular carcinoma in China: A multicenter retrospective analysis.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16192-e16192
Author(s):  
Qicong Mai ◽  
Song Chen ◽  
Feng Shi ◽  
Zhiqiang Mo ◽  
Jian He ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Real World ◽  
Objective Response ◽  
Progression Free Survival ◽  
Tumor Burden ◽  
Phase Iii ◽  
Advanced Hepatocellular Carcinoma ◽  
First Line ◽  
Grade 3

e16192 Background: Lenvatinib has been approved as a first-line systemic for advanced hepatocellular carcinoma (HCC) after the randomized phase III REFLECT trial. The aim of this study was to assess the lenvatinib-base treatment patterns and safety in real-world clinical settings in China. Methods: In this multicenter retrospective study, A total of 278 patients with unresectable HCC were treated with lenvatinib-base treatment between October 2018 and November 2020 were analyzed. Therapeutic effect was determined using the RECIST 1.1 and mRECIST criteria. Progression free survival (PFS), overall survival (OS) and treatment-related adverse events (TRAE) were also evaluated. Results: Of 278 unresectable HCC patients (median age: 56.1±11.9 years), 220 (79.1%) had cirrhosis caused by HBV infection. 215 (77.3%) and 63 (22.7%) patients were classified as Child-pugh A and B class, respectively. 233 (83.8%) and 45 (16.2%) patients received lenvatinib in first-line and second-line systemic therapies, respectively. 223 (80.2%) patients were treated with lenvatinib plus arterially directed therapy (TACE or HAIC of FOLFOX) and 55 (19.8%) were treated with lenvatinib alone. The objective response rate were 34.9% (RECIST) and 47.5% (mRECIST), while the disease control rate were 75.5%. With a median follow-up period of 12.8 months, the median PFS and OS were 7.8 months (95% CI 7.1–8.4) and 17.2 months (95% CI 14.9–19.6), respectively. Results from the multivariate analysis showed that the significant independent favorable prognosis factors were tumor burden< 50% (P=0.033), Child–Pugh A class (P<0.01), AFP level <200ng/mL (P=0.045), the combination with lenvatinib and arterially directed therapy (P<0.01). TRAE occurred in 219 of 278 patients (78.8%), most common TRAE were hypertension (n=118; 42.4%) and hand-foot skin reaction (n=91; 32.7%). The most common grade 3–4 TARE were hypertension (n=23; 8.3%), decreased appetite (n=18; 6.5%), AST elevation (n=14; 5%), and diarrhea (n=14; 5%) across all study patients. Conclusions: In this multicenter real-world study, lenvatinib-base treatment could be accomplished with well tolerated and response for unresectable HCC patients. Combination with arterially directed therapy could likely improve the overall survival.

scholarly journals Long-term prognostic value of sentinel lymph node tumor burden in survival of melanoma patients

2021 ◽  
pp. 1-5
Author(s):  
Mikko Vuoristo ◽  
Timo Muhonen ◽  
Virve Koljonen ◽  
Susanna Juteau ◽  
Micaela Hernberg ◽  
...  
Keyword(s):  
Lymph Node ◽  
Sentinel Lymph Node ◽  
Prognostic Value ◽  
Tumor Burden ◽  
Melanoma Patients

266 Tumour mutation burden (TMB) and efficacy outcomes in the phase III DANUBE study of advanced urothelial carcinoma (UC)

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A292-A292
Author(s):  
Sophie Wildsmith ◽  
Jill Walker ◽  
Anne L’Hernault ◽  
Weimin Li ◽  
Hannah Bye ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Stage Iv ◽  
Small Cell ◽  
Phase Iii ◽  
Survival Outcomes ◽  
Line Treatment ◽  
Small Cell Lung ◽  
First Line ◽  
Unresectable Stage ◽  
First Line Treatment

BackgroundThe phase III DANUBE study assessed the efficacy of the PD-L1 inhibitor durvalumab (D), alone or in combination with the CTLA-4 inhibitor tremelimumab (T), versus standard of care chemotherapy (SoC) for the first-line treatment of unresectable, locally advanced or metastatic UC. The study did not meet its co-primary endpoints of improving overall survival (OS) for D monotherapy vs SoC in patients with high tumor PD-L1 expression or for D+T vs SoC in the intention-to-treat population.1 TMB measurement in blood (bTMB) or tumour (tTMB) has been linked to improved efficacy with PD-1/PD-L1 inhibitors in UC and with D+T in non-small cell lung cancer,2 thus providing a rationale to explore TMB in the DANUBE trial.MethodsBaseline plasma samples from DANUBE were assessed for bTMB using the Guardant OMNI platform, while baseline tTMB was measured in formalin-fixed paraffin-embedded (FFPE) tumour samples using the FoundationOne CDx gene panel. Associations between progression-free survival (PFS) and median and landmark OS with bTMB and tTMB levels at various cutoffs were assessed as part of a pre-specified exploratory analysis. The data cutoff occurred on January 27, 2020.ResultsAmong 1032 patients randomised in DANUBE, 536 (51.9%) were evaluable for bTMB and 623 (60.4%) were evaluable for tTMB. For D vs SoC, bTMB and tTMB were not associated with OS or PFS at any cutoff. For D+T, stronger associations between bTMB and OS as well as PFS were observed with increasing bTMB cutoffs (table 1). At the bTMB cutoff ≥ 24 mut/Mb, 12-month OS rates were 76.7% for D+T and 54.3% for SoC, whereas for bTMB < 24 mut/Mb, 12-month OS rates were 53.4% for D+T and 51.2% for SoC. Similar trends for both OS and PFS were observed with tTMB (table 1).Abstract 266 Table 1Association between TMB and survival outcomes with D+TAssociation between TMB and survival outcomes with D+TConclusionsBoth bTMB and tTMB are potentially useful biomarkers for enriching responses to D+T in previously untreated, advanced UC. Neither bTMB nor tTMB was associated with better outcomes for D monotherapy. Cutoffs of 24 mut/Mb for bTMB and 10 mut/Mb for tTMB appear optimal for D+T in the setting of previously untreated, advanced UC.Trial RegistrationThe trial is registered with ClinicalTrials.gov, NCT02516241, and the EU Clinical Trials Register, EudraCT number 2015-001633-24.ReferencesAstraZeneca. Update on phase III DANUBE trial for IMFINZI and tremelimumab in unresectable, stage IV bladder cancer [press release] March 6, 2020. [https://www.astrazeneca.com/media-centre/press-releases/2020/update-on-phase-iii-danube-trial-for-imfinzi-and-tremelimumab-in-unresectable-stage-iv-bladder-cancer-06032020.html]Rizvi NA, Cho BC, Reinmuth N, et al. Durvalumab with or without tremelimumab vs standard chemotherapy in first-line treatment of metastatic non-small cell lung cancer: The MYSTIC phase 3 randomized clinical trial. JAMA Oncol. 2020:6:661–674.Ethics ApprovalThe study protocol was approved by the Ethics Board at each investigator’s institution.

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