OS Benefit Research Articles

Efficacy of adjuvant radiation in early-stage cancers of buccal mucosa: an institutional experience.

The purpose of this study is to determine if depth of infiltration is the only risk factor that will determine the outcomes in early-stage buccal mucosa patients or do the other minor risk factors have an impact too. It is a retrospective analysis of 226 patients with early-stage buccal mucosa cancer who were treated with curative intent from 2010 to 2020. These patients were grouped in two arms, surgery alone (n = 111) and surgery followed by adjuvant radiotherapy (n = 115). Patients were followed up and local and regional recurrences and distant metastasis were recorded. Our results show that addition of radiation to the standard surgery arm improves overall survival and disease-free survival, though the improvement in overall survival was not statistically significant. This improvement was more pronounced in the depth of infiltration > 5mm and in 5mm or less depth of infiltration this benefit was not statistically significant. Other factors like perineural invasion, lymphovascular invasion, tumour size, node positive, margin positive were considered for univariate analysis. Although there was a trend towards improvement of OS and DFS, it was not statistically significant as far as these factors are concerned. The role of adjuvant radiation in early-stage cancers of buccal mucosa is a crucial tool with definitive DFS benefit and requires more prospective trials to answer the OS benefit.

Evidence of clinical benefit of WHO essential anticancer medicines for children, 2011-2021.

Access to essential cancer medicines is a key determinant of childhood cancer survival. WHO published the Model List of Essential Medicine for Children (EMLc) and updated it every two years since 2007 to promote better access to medicines for children. This study aimed to assess whether the inclusion of essential anticancer medicines for respective indications for children was based on evidence of significant clinical benefit between 2011 and2021. We identified all anticancer medicine indications added to the WHO EMLc Section 8 since 2011 and extracted evidence of benefit documented in the corresponding technical reports. Evidence in children was defined as evidence that included participants under 12, and graded into five levels, according to the Oxford Centre for Evidence-Based Medicine Levels of Evidence. We analyzed whether each anticancer medicine indication was listed with documented OS benefit or improvements in surrogate measures based on the highest level of documented evidence in children. A total of 115 anticancer medicine indications were added to the EMLc from 2011 to 2021, of which 101 (87.8%) had some clinical evidence in children and 4 (3.5%) were added without any clinical evidence. Among the 101 medicine indications, none were added with level-1 evidence in children, and 43 (42.6%), 11 (10.9%), 41 (40.6%), and 6 (5.9%) were listed with level-2, level-3, level-4, and level-5 evidence in children, respectively. Only eight (7.9%) medicine indications were reported to have OS benefit, another 12 (11.9%) were reported to have improvements on surrogate measures, and 81 (80.2%) were listed in the EMLc without documented improvements in either OS or surrogate measures. Most anticancer medicine indications of the WHO EMLc were added based on limited evidence of statistically significant clinical benefit in children. Our results suggest that WHO should refine requirements for clinical benefit criteria and permissible forms, quality, and reporting of evidence of essential anticancer medicines for children, specify whether anticancer medicine indications have required evidence of clinical benefit in children, and provide further details in its technical reports that summarise the available evidence. Not applicable.

Clinical Outcomes With Pembrolizumab-Based Therapies in Recurrent/Refractory NSCLC After Chemoradiation and Consolidative Durvalumab

BackgroundOften, patients with NSCLC experience recurrent/refractory (R/R) disease within 2 years of chemoradiation (CRT) and consolidative durvalumab. Despite prior immune checkpoint inhibitor exposure, immunotherapy with or without chemotherapy is typically initiated if a driver-oncogene is absent. However, there remains a paucity of data regarding the efficacy of immunotherapy in this patient population. Here, we present survival outcomes associated with pembrolizumab for R/R NSCLC. Materials and MethodsWe retrospectively assessed adults with NSCLC who received pembrolizumab for R/R disease between January 2016 to January 2023. Primary objective was to estimate OS and PFS in this cohort compared to historical outcomes. Secondary objective was to compare OS and PFS among subgroups. ResultsFifty patients were evaluated. Median follow-up time was 11.3 months (2.9-38.2). OS was 10.6 months (95% CI, 8.8-19.2); 1-year OS rate 49% (95% CI, 36 - 67%). PFS was 6.1 months (95% CI, 4.7-9.0); 1-year PFS rate 25% (95% CI, 15%-42%). Current smokers had significantly better median OS/PFS as compared to former smokers (NA vs. 10.5 and 9.9 vs. 6.0 months, respectively). The addition of chemotherapy demonstrated an OS benefit (median OS 12.9 vs. 6.0 months) but was not statistically significant. ConclusionPatients with R/R NSCLC represent a distinct cohort with inferior survival outcomes when compared to those with de novo stage IV disease treated with pembrolizumab-based regimens. Based on our findings, we recommend oncologists exercise caution when considering checkpoint inhibitor monotherapy in the front-line setting for R/R NSCLC, regardless of PD-L1 expression.

Abstract CT080: Tremelimumab (T) + durvalumab (D) + chemotherapy (CT) in 1L metastatic NSCLC: Outcomes by blood tumor mutational burden (bTMB) in POSEIDON

Abstract Background: In the Phase 3 POSEIDON study (NCT03164616), 1L T plus D and platinum-based CT demonstrated statistically significant improvements in both PFS (HR, 0.72; 95% CI, 0.60-0.86; p=0.0003; data cutoff [DCO] July 24, 2019) and OS (HR, 0.77; 95% CI, 0.65-0.92; p=0.0030; DCO March 12, 2021) vs CT in patients (pts) with EGFR/ALK wild-type metastatic (m) NSCLC. On the basis of these results, T+D+CT was approved by the FDA in November 2022 for use in this setting. Here we report outcomes in POSEIDON pt subgroups defined by a range of bTMB values, including a pre-specified cutoff of 20 mutations/megabase (mut/Mb). Methods: Pts were randomized 1:1:1 to 1L T+D+CT (platinum-based), D+CT or CT, with stratification by tumor cell (TC) PD-L1 expression (TC ≥50% vs <50%; VENTANA PD-L1 [SP263] assay), disease stage (IVA vs IVB) and histology (squamous vs non-squamous). bTMB was assessed using the GuardantOMNI platform. OS, PFS and ORR with T+D+CT vs CT were determined for pts with bTMB ≥ vs <20 mut/Mb. Outcomes across additional bTMB cutoffs (10, 12 and 16 mut/Mb) were also explored. Results: Plasma samples were available for 958/1013 pts from the intention-to-treat (ITT) population. Of those with available plasma samples, 81.8% (784/958) were evaluable for bTMB, including 277 in the T+D+CT arm and 241 in the CT arm. Similar demographic characteristics and OS were observed in the bTMB evaluable vs ITT populations. Consistent with previous reports, the proportion of never smokers was higher in the bTMB <20 mut/Mb subgroup than in the bTMB ≥20 mut/Mb subgroup. Across all bTMB cutoffs analyzed, OS and PFS benefit for T+D+CT vs CT were generally consistent with the ITT population in both bTMB high and bTMB low subgroups. However, at each bTMB cutoff, OS and PFS benefit appeared more prominent among pts in the bTMB high subgroups. Median OS (mOS) was longer with T+D+CT vs CT in both the bTMB ≥20 mut/Mb and <20 mut/Mb subgroups and HRs suggested more pronounced benefit in the bTMB high group. mOS was 13.5 months with T+D+CT vs 10.3 months with CT (unstratified HR, 0.61; 95% CI, 0.42-0.88) for pts with bTMB ≥20 mut/Mb and 12.6 months vs 10.9 months (unstratified HR, 0.79; 95% CI, 0.63-0.99) for pts with bTMB <20 mut/Mb. PFS and ORR showed similar trends to OS (data will be presented). In both subgroups with PD-L1 TC ≥1% or <1%, HRs suggested more pronounced OS/PFS benefit in pts with bTMB ≥20 (vs <20) mut/Mb (data will be presented). Conclusions: In pts with mNSCLC, treatment with a limited course of T plus D (until progression) and four cycles of CT consistently improved clinical outcomes vs CT alone in both bTMB high and low subgroups, supporting the use of this regimen as a 1L treatment option for pts with mNSCLC. The clinical benefit vs CT appeared to be greater in pts with higher bTMB over a range of cutoffs, consistent with expectations based on mechanistic biology and previous clinical data. Citation Format: Solange Peters, Hisani Madison, Kelly Oliner, Anne L’Hernault, Marianne Ratcliffe, Karen Barrett, Xiaojin Shi, Edward B. Garon, Tony Mok, Melissa L. Johnson. Tremelimumab (T) + durvalumab (D) + chemotherapy (CT) in 1L metastatic NSCLC: Outcomes by blood tumor mutational burden (bTMB) in POSEIDON [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT080.

PD44-09 IMPACT OF HIGH-RISK FEATURES AND STAGING ON NEOADJUVANT CHEMOTHERAPY AMONG PATIENTS TREATED WITH RADICAL CYSTECTOMY: A SINGLE CENTER ANALYSIS OF 1700 CASES

You have accessJournal of UrologyCME1 Apr 2023PD44-09 IMPACT OF HIGH-RISK FEATURES AND STAGING ON NEOADJUVANT CHEMOTHERAPY AMONG PATIENTS TREATED WITH RADICAL CYSTECTOMY: A SINGLE CENTER ANALYSIS OF 1700 CASES Shreyas Naidu, Roger Li, Wenyi Fan, Kyle Rose, Heather Huelster, Aram Vosoughi, Scott Gilbert, Daniel Grass, Rohit Jain, Youngchul Kim, Brandon Manley, Michael Poch, Julio Pow-Sang, Philippe Spiess, Alice Yu, Logan Zemp, Jingsong Zhang, and Wade Sexton Shreyas NaiduShreyas Naidu More articles by this author , Roger LiRoger Li More articles by this author , Wenyi FanWenyi Fan More articles by this author , Kyle RoseKyle Rose More articles by this author , Heather HuelsterHeather Huelster More articles by this author , Aram VosoughiAram Vosoughi More articles by this author , Scott GilbertScott Gilbert More articles by this author , Daniel GrassDaniel Grass More articles by this author , Rohit JainRohit Jain More articles by this author , Youngchul KimYoungchul Kim More articles by this author , Brandon ManleyBrandon Manley More articles by this author , Michael PochMichael Poch More articles by this author , Julio Pow-SangJulio Pow-Sang More articles by this author , Philippe SpiessPhilippe Spiess More articles by this author , Alice YuAlice Yu More articles by this author , Logan ZempLogan Zemp More articles by this author , Jingsong ZhangJingsong Zhang More articles by this author , and Wade SextonWade Sexton More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003354.09AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Neoadjuvant chemotherapy (NAC) followed by radical cystectomy with pelvic lymph node dissection (RC) has convincingly demonstrated improvement in survival and consequently been established as the new standard-of-care for muscle invasive bladder cancer (MIBC). Due to its toxicity, multi-agent platinum-based chemotherapy has been variably adopted in the neoadjuvant setting. In this study, we report the long-term outcomes from our institutional experience with the use of NAC in MIBC patients METHODS: 1700 patients who underwent RC at Moffitt Cancer Center between July 2004 and October 2020 for bladder cancer were retrospectively reviewed. Patients received presurgical chemotherapy and radical cystectomy (PC) or underwent upfront radical cystectomy with no chemotherapy (NC). cT2 patients were sub-stratified as high-risk (HR) or low-risk (LR) using the MDACC risk criteria including the presence of hydronephrosis, LVI, prostatic urethral involvement, and variant histology. RESULTS: 761 PC and 805 NC patients were retrospectively identified with complete baseline information. Amongst 461 NC patients with ≥cT2 disease, 118 (25%) achieved pathologic downstaging<pT2N0 and 38 (8.2%) pCR. In comparison, 244 (35.8%) PC patients with ≥cT2 disease achieved pathologic downstaging (p<0.001) and 135 (19.8%) pCR (p<0.0001). Stratified by clinical T-stage, only cT2 patients derived OS (Median 62.3mo vs. 41.9mo, p<0.001) benefit. To further categorize the characteristics associated with superior chemotherapeutic response, we sub-stratified the cT2 patients according to the MDACC risk criteria. While the use of PC in low-risk (LR) cT2 patients did not significantly increase downstaging (42.7% vs. 34.4%) or pCR (23.5% vs. 11.9%) rates, dramatic increases were seen in the high risk (HR) cT2 patients undergoing PC (downstaging 41.6% vs. 19.4%, p<0.0001; pCR 23.5% vs. 6.9%, p<0.0001). CONCLUSIONS: Pathologic response rates to PC were modest compared to those previously reported in randomized controlled trials and only cT2 patients derived OS benefit among those that received PC. Upon further analysis it was found that following stratification using the MDACC risk criteria, only HR cT2 patients obtained a benefit from presurgical chemotherapy. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e1128 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Shreyas Naidu More articles by this author Roger Li More articles by this author Wenyi Fan More articles by this author Kyle Rose More articles by this author Heather Huelster More articles by this author Aram Vosoughi More articles by this author Scott Gilbert More articles by this author Daniel Grass More articles by this author Rohit Jain More articles by this author Youngchul Kim More articles by this author Brandon Manley More articles by this author Michael Poch More articles by this author Julio Pow-Sang More articles by this author Philippe Spiess More articles by this author Alice Yu More articles by this author Logan Zemp More articles by this author Jingsong Zhang More articles by this author Wade Sexton More articles by this author Expand All Advertisement PDF downloadLoading ...

A systematic review of neoadjuvant and definitive immunotherapy in locally advanced head and neck squamous cell carcinoma.

Patients with locally advanced head and neck squamous cell carcinoma (HNSCC) require multi-modality treatment. Immune checkpoint inhibitors (ICIs) are now standard of care in management of recurrent/metastatic HNSCC. However, its role in the definitive and neoadjuvant setting remains unclear. A literature search was conducted that included all articles investigating ICI in untreated locally advanced (LA) HNSCC. Data was extracted and summarised and rated for quality using the Cochrane risk of bias tool. Of 1086 records, 29 met the final inclusion criteria. In both concurrent and neoadjuvant settings, the addition of ICI was safe and did not delay surgery or reduce chemoradiotherapy completion. In the concurrent setting, although ICI use demonstrates objective responses in all published trials, there has not yet been published data to with PFS or OS benefit. In the neoadjuvant setting, combination ICI resulted in superior major pathological response rates compared to ICI monotherapy without a significant increase adverse event profiles, but its value in improving survival is not clear. ICI efficacy appears to be affected by tumour characteristics, in particular PD-L1 combined positive score, HPV status and the tumour microenvironment. There is significant heterogeneity of ICI use in untreated LA HNSCC with multiple definitive concurrent and neoadjuvant protocols used. Resultantly, conclusions regarding the survival benefits of adding ICI to standard-of-care regimens cannot be made. Further trials and translational studies are required to elucidate optimal ICI sequencing in the definitive setting as well as better define populations more suited for neoadjuvant protocols.

Abstract OT1-21-01: Preoperative radiotherapy and systemic therapy following surgery in ‘de novo’ metastatic breast cancer (Protocol MF22-01; Intervention Systemic Treatment METastasis-ISTMET)

Abstract Background Five to eight percent of breast cancer (BC) patients present with distant metastasis at diagnosis, known as ‘de Novo’ metastatic breast cancer (dnMBC). Recent data showed that approximately 40% of dnMBC patients undergo locoregional treatment (LRT). LRT treatment modalities for metastasis and primary tumor benefit a subset of patients with oligometastatic disease. Our study group has recently demonstrated two prospective studies regarding this topic with favorable outcomes. MF07-01 IMET study, one of the first clinical randomized trials, showed that the patients with the diagnosis of dnMBC undergoing LRT followed by systemic therapy had an additional 14% OS benefit by the end of the 10-year follow-up when compared with others who received only systemic therapy. A prospective multicenter registry study MF14-01 BOMET also presented LRT prolonged survival and decreased locoregional recurrence in a prospective registry study with a median follow-up of 3 years. Timing of primary breast surgery either at diagnosis or after systemic treatment provided a survival benefit similar to systemic therapy alone in bone-only dnMBC patients. Although, the optimal timing of concurrent endocrine therapy, radiotherapy, and/or sequential surgery remains unclear. Hypothesis We hypothesize that in the era of modern radiotherapy and endocrine therapy, concurrent radiation and endocrine therapy will be non-inferior to sequential treatment modalities in terms of locoregional and systemic disease control in dnMBC. ER/PR (+), Her2 neu (-) oligometastatic dnMBC patients are potentially curable with multimodality treatments. Objectives The primary objective is to perform a Phase I study to evaluate the feasibility of this curative intent treatment approach for patients with oligometastatic disease. Secondary objectives are to present the treatment response evaluating with CTC and/or ctDNA, and IHC and marker changes with multimodality treatments Methods Postmenopausal ER/PR (+) and Her2 neu (-), oligometastatic dnMBC patients will be enrolled in the study. Inclusion criteria: Primary breast tumor amenable for complete surgical resection, patients in good physical condition for receiving protocol-driven locoregional and systemic treatments and radiotherapy; Bone-only oligometastatic disease (5 or less metastasis); Primary tumor biopsy, metastatic site biopsy (ER/PR, Her2, Ki67). Exclusion criteria: Primary tumor not amenable for complete resection; primary tumor with extended infection, bleeding, or necrosis; patients with poor physical condition which prevents the patient from receiving protocol-driven locoregional and systemic treatment; synchronous primary cancer at the contralateral breast; clinically involved contralateral axillary nodes; patients not suitable for adequate follow-up, and failure to give informed consent. Study Design: • RT to the primary tumor (Hypo fractionated) + AI concurrent, Collect CTC and/or ctDNA • Add CDK4/6i to AI 2-4 weeks after RT + (6 months) • RT to bone metastasis (if still visible), Collect CTC and/or ctDNA + (12 months) • Primary Breast Surgery, Collect CTC and/orctDNA, ER/PR/Her 2 in the final specimen + • CDK4/6i +AI until progression and/or unmanageable toxicity Conclusion We hypothesize that in the era of modern radiotherapy and endocrine therapy, concurrent radiation and endocrine therapy will be non-inferior to sequential treatment modalities in terms of locoregional and systemic disease control in dnMBC. ER/PR (+), Her2 neu (-) oligometastatic dnMBC patients are potentially curable with multimodality treatments. Citation Format: Atilla Soran, Serdar Ozbas, Lutfi Dogan, Kamuran İbis, Mutlu Dogan, M Selam, Kazim Senol, Secil Ak Aksoy, Mine Ozsen, Sibel Cetintas, Turkkan Evrensel, Efe Sezgin. Preoperative radiotherapy and systemic therapy following surgery in ‘de novo’ metastatic breast cancer (Protocol MF22-01; Intervention Systemic Treatment METastasis-ISTMET) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT1-21-01.

Abstract P4-01-42: Pooled analysis of post-progression treatments after first-line ribociclib + endocrine therapy in patients with HR+/HER2− advanced breast cancer in the MONALEESA-2, -3, and -7 studies

Abstract Background: The MONALEESA (ML) studies showed significant PFS &amp; OS benefits for 1L ribociclib (RIB) + endocrine therapy (ET) in patients (pts) with pre/peri &amp; postmenopausal advanced breast cancer. The benefit of RIB beyond study treatment (tx) was also observed, with improvements in PFS2 &amp; delays in time to 1st subsequent chemotherapy (CT). While there is currently no preferred tx for the next line post-progression on a CDK4/6 inhibitor (CDK4/6i), except alpelisib in pts with a PIK3CA mutation, guidelines encourage multiple lines of ET or ET-based therapies before switching to CT (except for visceral crisis). This pooled exploratory analysis of the ML studies examined outcomes of various tx strategies post progression on RIB + ET. Methods: Data from pts receiving 1L therapy in ML-2, -3, &amp; -7 (NSAI cohort only &amp; excluding pts with early relapse [≤ 12 mo after end of (neo)adjuvant ET] whose prognosis is closer to that of 2L pts) were pooled &amp; pts receiving 1st subsequent therapies after progression were analyzed. Three groups of subsequent therapies were assessed: ET only, CT, &amp; targeted therapy. Subsequent CT comprises CT +/- any other therapy; targeted therapy includes CDK4/6i, mTORi, PI3Ki, AKTi, etc, +/- ET. Subsequent CT &amp; targeted therapy groups are mutually exclusive. Median duration of study tx, 1st subsequent therapy, &amp; OS (from randomization to death) were analyzed by KM methods. Weighted Cox regressions were performed using inversed propensity scoring matching method (inverse probability tx weighting [IPTW]) to ensure compatible pt characteristics between tx arms. These are not randomized comparisons; only baseline characteristics were used for the estimation of propensity scores in the IPTW, imbalance of prognostic factors at progression may exist. Results: Median follow-up time was 74 mo. 461 pts treated with RIB (81%) &amp; 440 (86%) with PBO discontinued study tx &amp; received a subsequent therapy. In the RIB arms, the most common 1st subsequent therapies were ET only (40%), CT (29%), combination with targeted therapy (28%), &amp; other (4%); for the PBO arms, 34% received CT as a 1st subsequent therapy &amp; 31% each received ET only or combination with targeted therapy (5% received other). In 14% &amp; 20% of pts in the RIB &amp; PBO arms, the 1st subsequent therapy was a CDK4/6i, of these 31% &amp; 12% were RIB. In general, regardless of type of 1st subsequent therapy, the duration of both the study tx &amp; the 1st subsequent therapy was longer for pts treated with RIB vs PBO (Table). In both RIB &amp; PBO arms, pts who received subsequent CT had the shortest duration on study tx, whereas those who received subsequent targeted therapy combination had the longest. Among pts on 1L RIB + ET, after matching pre-randomization baseline characteristics, subsequent CDK4/6i use was associated with the longest mOS (84 [84-NE] mo), followed by ET only (60 [51-68] mo), then a non-CDK4/6i targeted therapy (52 [43-72] mo); post-progression CT was associated with the shortest mOS (37 [32-48] mo). Conclusions: This large, pooled analysis of the ML studies shows that, in general, duration of any subsequent therapy was numerically longer post-1L RIB + ET vs PBO + ET, &amp; subsequent CT was used less frequently for pts on RIB vs PBO. Both findings confirm that upfront tx with RIB does not worsen pt outcomes. This trend in enhancement of outcomes of subsequent therapies seen with 1L RIB suggests a post-tx effect that merits further exploration. Citation Format: Erika Hamilton, Laura M. Spring, Peter A. Fasching, Sandra Franco, Richard H DeBoer, Javier Cortés, Kevin Kalinsky, Dejan Juric, Aditya Bardia, Sina Haftchenary, Agnes Lteif, Juan Pablo Zarate, Liyi Cen, Patrick Neven. Pooled analysis of post-progression treatments after first-line ribociclib + endocrine therapy in patients with HR+/HER2− advanced breast cancer in the MONALEESA-2, -3, and -7 studies [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-01-42.

Let’s Write a Comic Together! Exploring Peer Collaborative Writing in EFL Secondary Mixed-age Classrooms

Based on the beliefs (assertions) that students benefit socially and cognitively from interacting with peers of different ages, mixed-age (M-A) classrooms have attracted much attention from educators, education policymakers, and researchers. Nevertheless, research into the role and impact of age grouping in second (L2) and foreign language (FL) learning is rather scarce. Moreover, a growing body of research has shown that by linking oral and written modes, collaborative writing (CW) aids language learning. However, the majority of studies have investigated adult and young adult students, and very few were conducted with secondary and high school students. Based on our knowledge, no study has explored CW in M-A secondary school classrooms. With these research gaps in mind, and drawing predominantly on documentary analysis of student written work, the present study examined CW of 28 students of English as a foreign language (EFL) aged 12 to 15 old learners who jointly wrote a comic. The findings point to limitations of M-A peer interaction suggesting that there is a threshold for the younger learners in terms of benefiting from CW with their older partners. Similarly, the findings suggest that the extent to which OS benefit is rather limited.

Niraparib (NIRA) with abiraterone acetate and prednisone (AAP) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) and homologous recombination repair (HRR) gene alterations: Second interim analysis (IA2) of MAGNITUDE.

170 Background: In the primary analysis of the phase 3 MAGNITUDE study, NIRA/AAP significantly improved outcomes in pts with mCRPC and HRR gene alterations. Here, we report results from IA2 of secondary endpoints in MAGNITUDE. Methods: 423 eligible pts with mCRPC and HRR alterations (HRR+ cohort) were randomized 1:1 to receive NIRA/AAP (n = 212) or placebo (PBO)/AAP (n = 211). At the prespecified IA2, secondary endpoints (time to cytotoxic chemotherapy [TCC], time to symptomatic progression [TSP], overall survival [OS]) were formally assessed and the primary rPFS endpoint was updated in the HRR+ cohort, with sensitivity analysis performed for the subgroup of pts with BRCA alterations. Results: Updated descriptive rPFS results at IA2 (cutoff: June 17, 2022) were consistent with the primary analysis in the HRR+ cohort. In the BRCA subgroup, NIRA/AAP extended median rPFS to 19.5 mos vs 10.9 mos with PBO/AAP. NIRA/AAP led to statistically significant benefit in TSP in the HRR+ cohort with consistent benefit in the BRCA subgroup. Continued consistent improvement of TCC was seen with NIRA/AAP in the HRR+ cohort and in the BRCA subgroup. There was a trend towards improved OS with NIRA/AAP in the BRCA subgroup in the primary stratified analysis and the multivariate analysis (MVA), accounting for imbalances in key baseline characteristics. BRCA pts treated with NIRA/AAP experienced delayed time to worst pain intensity (HR, 0.70; 95% CI, 0.44, 1.12; nominal P = 0.1338) and pain interference (HR, 0.67; 95% CI, 0.40, 1.12; nominal P = 0.1275) compared to PBO/AAP. The safety profile at IA2 was consistent with that of the primary analysis, with no new safety signals observed. Conclusions: With 26.8 months of median follow-up, there was a statistically significant and meaningful clinical benefit in TSP and meaningful clinical benefit in TCC. Additionally, updated rPFS results from MAGNITUDE IA2 were consistent with the primary analysis; OS benefit was not conclusive due to immaturity and will be followed through to final analysis. Taken together, these data continue to support the use of NIRA/AAP in pts with mCRPC and BRCA alterations or select other HRR gene alterations. Clinical trial information: NCT03748641 . [Table: see text]

Atezolizumab (atezo) + platinum/gemcitabine (plt/gem) vs placebo + plt/gem for first-line (1L) treatment (tx) of locally advanced or metastatic urothelial carcinoma (mUC): Final OS from the randomized Phase 3 IMvigor130 study.

LBA440 Background: The IMvigor130 primary analysis demonstrated statistically significant PFS benefit with 1L atezo + plt/gem (Arm A) vs placebo + plt/gem (Arm C) in pts with mUC (Galsky Lancet 2020). Interim data showed improved OS with Arm A vs C but did not cross the pre-specified threshold for significance (Galsky Lancet 2020; Galsky AACR 2021). In exploratory analyses, OS improved when atezo was combined with cisplatin (cis) vs carboplatin (carbo) regardless of PD-L1 status. Here, we report final OS data from Arms A and C. Methods: Pts were randomly assigned 1:1:1 to Arm A, B (atezo alone) or C. Arm A and C pts received cis or carbo per investigator (INV) choice. Co-primary endpoints were PFS per INV RECIST 1.1 and OS (Arm A vs C), and OS (Arm B vs C), tested hierarchically. Safety, ORR and DOR, disease control rate (DCR; confirmed CR, PR or [SD ≥ 6 mo]) and pre-specified exploratory OS data are also reported. Results: As of data cutoff Aug 31, 2022 (49 mo since last pt randomly assigned), in ITT pts, OS benefit was not statistically significant; in the cis subgroup, HR was 0.76 (95% CI 0.57, 1.01; Table). In ITT pts, DCR was 65% (290/447) in Arm A and 60% (239/397) in Arm C. 81% of safety-evaluable pts (370/454) in Arm A and 80% (312/389) in Arm C had a Gr 3/4 tx-related AE (TRAE). Gr 5 TRAEs occurred in 9 pts (2%) in Arm A and 4 (1%) in Arm C; Gr 3/4 AEs of special interest were seen in 41 pts (9%) in Arm A and 17 (4%) in Arm C. Conclusions: In this final analysis, improved OS with atezo + plt/gem vs placebo + plt/gem did not reach statistical significance in ITT pts with mUC. As seen with prior exploratory data, improved OS with atezo + plt/gem was greater when pts received cis vs carbo. No new safety signals were seen. Clinical trial information: NCT02807636 . [Table: see text]

A platform for high-resolution immune liquid biopsy analysis to predict response in patients with renal cell carcinoma treated with nivolumab or cabozantinib: Preliminary data from I-RENE trial (Meet-URO 8 study).

712 Background: Nivolumab, an immune checkpoint inhibitor of PD-1, demonstrated a significant OS benefit in patients with metastatic renal cell carcinoma (mRCC), in progression after a previous line of therapy with anti-VEGFR agents. However, the features of effective immune response and predictive biomarkers of clinical benefit to PD-1 blockade have not yet been recognized. Methods: I-RENE is a prospective translational multicenter Italian study of a real-life mRCC patients treated with nivolumab or cabozantinib after failure of therapy with anti-VEGFR agents. 82 patients were enrolled from December 2018 to August 2022 (nivo 60, cabo 22), with blood samples obtained at baseline and at different time points in both treatment groups. An extended concept of "immune liquid biopsy" is being applied to the study, consisting in the phenotypic and transcriptional profile of lymphoid and myeloid subsets, immune-related miRNA quantification, cyto/chemo-kinome and RNAseq of extracellular vesicle. Results: Multiparametric flow cytometry, performed to monitor the blood frequency and different myeloid and lymphoid cells, show that monocyte subsets (classical, intermediate and non-classical CD14+ cells), monocytic myeloid derived suppressor cells (MDSC, such as CD14+HLA-DRneg and CD14+PD-L1+) and polymorphonucleate (PMN)-MDSC, remain either stable or increase during treatment; concomitantly, CD8+PD-1+ T cells (detected by anti-nivolumab IgG4) increment frequency, acquire the effector CD45RA-CCR7+ phenotype and express the proliferating marker Ki67. Patients receiving cabozantinib display instead a remarkable decrease of all myeloid cell subsets, paired by the boost of cytotoxic CD3-CD16+CD56dim NK cells and more marginally of CD8+PD1+ cells, Preliminary correlations indicate that clinical benefit of nivolumab seems to cluster with the lack of CD14+ cells and M-MDSC increase and blood frequency of total, and the boost in CD8+CD45RA-CCR7+Ki67+ effector T cells. In contrast, the cabozantinib-induced immune modulation occurring in patients treated with does not associate with clinical response Conclusions: This first set of data indicate blood as promising source of dynamic biomarkers for the development of algorithms predicting response to PD-1 blockade. Furthermore, the results so far collected suggest that the potent immunomodulation induced by cabozantinib on the immunosuppressive myeloid compartment may not lead to any tumor control in the absence of specific immune stimulation by checkpoint inhibitors. This study was supported by the Italian Ministry of health (RF-2016_02363001). Clinical trials.gov: NCT04891055 Clinical trial information: NCT04891055 .

Real-time evidence synthesis for first line (1L) treatment of metastatic renal cell carcinoma (mRCC): A living, interactive systematic review and Bayesian network meta-analysis.

695 Background: Recent results from COSMIC 313 trial and updated findings from other contemporary trials have added to the existing body of evidence for 1L mRCC. Therefore, we present the most up-to-date results from our living, interactive systematic review (LISR) to facilitate the choice of optimal therapy in 1L mRCC setting. Methods: This LISR and network meta-analysis is maintained using a novel living evidence synthesis (LIvE) framework. The framework facilitates the identification of new or updated studies using an automated ‘living’ search which is followed by screening and extraction in a semi-automated fashion within a machine learning assisted graphical user interface. Relevant data is parsed and analyzed to compute mixed treatment comparisons and certainty of evidence is adjudicated using a rule-based algorithm. Detailed methods have been published before (PMID: 33824031). Results: As of October 1st 2022, this LISR includes 16 clinical trials (30 references). Mixed treatment comparisons showed statistically significant PFS benefit with lenvatinib-pembrolizumab (LenPem; rank 1) when compared to cabozantinib-nivolumab (CabNivo; rank 3; hazard ratio [HR]: 0.69, 95% confidence interval: 0.52-0.93), CaboNivo-ipilimumab (CaboNivoIpi; rank 4; HR: 0.62; 0.43-0.89), avelumab-axitinib (AveAxi; rank 5; HR: 0.56; 0.43-0.75), PemAxi (rank 6; HR: 0.55; 0.42-0.72), atezolizumab-bevacizumab (AteBev; rank 7; HR: 0.46; 0.35-0.59), and NivoIpi (rank 8; HR: 0.45; 0.35-0.59). No significant differences were observed between CaboNivoIpi and other combination therapies for PFS improvement. Similarly, for OS, LenPem (rank 1), PemAxi (rank 2) and CaboNivo (rank 3) were ranked as potentially more efficacious treatment options than other counterparts. However, no statistically significant difference was observed for OS benefit with mixed treatment comparisons. The odds of achieving an ORR were higher with LenPem (rank 1; odds ratio [OR]: 2.44; 1.43-4.17), and CaboNivo (rank 2; OR: 1.77; 1.04-3.03) when compared to CaboNivoIpi (rank 6). NivoIpi (rank 1), LenPem (rank 2), CaboNivoIpi (rank 3) were ranked potentially as more efficacious treatments for achieving a CR. In terms of grade 3 or higher treatment related adverse events, NivoIpi (rank 3) was ranked as potentially the safest option among other combinations while CaboNivoIpi (rank 12), LenPem (rank 11), and CaboNivo (rank 10) were more likely to increase the risk of toxicity compared to most other treatments. Conclusions: Triplet combination of CaboNivoIpi may not provide additional survival benefit compared to other immunotherapy combinations and may increase toxicity. Patient-level considerations such as treatment toxicity, and quality of life should be factored in when opting intensified 1L therapies in mRCC patients.

Study EV-104: Phase 1 study of intravesical enfortumab vedotin for treatment of patients with non-muscle invasive bladder cancer (NMIBC)—Trial in progress.

TPS582 Background: The majority of patients with bladder cancer present with non-muscle invasive disease (Chang 2016; Woldu 2017; Kates 2020; Li 2020). The standard of care for treatment of high risk NMIBC involves transurethral resection of the bladder tumor (TURBT) followed by intravesical Bacillus Calmette-Guerin (BCG) or chemotherapy. Although the response rate to BCG therapy is high, many patients recur within 1–5 years (Matulay JU 2021). For patients who have BCG unresponsive disease after adequate course of BCG, there are limited options. While radical cystectomy (RC) is still considered the standard of care, most patients are reluctant to undergo RC and their options are limited to intravesical chemotherapy or pembrolizumab. Enfortumab vedotin (EV) is an antibody-drug conjugate directed to Nectin-4, which is highly expressed in bladder tumors. In EV-301, a phase 3 study, EV showed an OS benefit vs chemotherapy in patients with locally advanced or metastatic urothelial carcinoma (la/mUC) who had previously received platinum-based therapy and a PD-1 or PD-L1 inhibitor (Powles NEJM 2021). Based on its demonstrated benefit in la/mUC, EV is currently being evaluated in earlier UC settings. The purpose of this study is to investigate the intravesical administration of EV for patients with NMIBC. Methods: EV-104 (NCT05014139) is a phase 1, open-label, multicenter, dose-escalation and dose-expansion study designed to evaluate the safety, tolerability, PK, and antitumor activity of intravesical EV in adults with high-risk BCG-unresponsive NMIBC (carcinoma in situ with or without papillary disease) who are ineligible for or refuse RC. The dose escalation part of the trial aims to identify the maximum tolerated dose (MTD) and/or recommended dose of intravesical EV. The dose expansion part will evaluate patients at the MTD or recommended dose and further characterize safety and antitumor activity of intravesical EV. The study treatment regimen will include an induction phase, where patients will receive intravesical EV weekly for 6 weeks followed by monthly maintenance for a total of 9 additional EV doses. Patients will be assessed for response every 3 months by cystoscopy and urine cytology, while on study. Safety and antitumor activity endpoints will be summarized using descriptive statistics. The study is currently enrolling in the US with additional sites planned in Canada and the EU. Clinical trial information: NCT05014139 .

No survival benefit with suboptimal CA19-9 response: defining effective neoadjuvant chemotherapy in resectable or borderline resectable pancreatic cancer

Background/purposeNeoadjuvant chemotherapy (NAC) is gaining popularity over a surgery-first (SF) approach in treating resectable and borderline resectable pancreatic ductal adenocarcinoma (PDAC). However, what constitutes effective neoadjuvant chemotherapy is unknown. MethodsWe retrospectively analyzed resectable and borderline resectable PDAC patients who underwent pancreaticoduodenectomy (2010–2019) at a single institution. Optimal CA19-9 response was defined as normalization AND >50% reduction. We utilized Kaplan-Meier and multivariable-adjusted Cox models and competing risk subdistribution methods for statistical analysis. Results586 patients were included in this study. The multivariable-adjusted analysis demonstrated OS benefit in the NAC group only when OS was calculated from diagnosis (HR = 0.72, p = 0.02), but not from surgery (HR = 0.81, p = 0.1). However, in 59 patients who achieved optimal CA19-9 response, OS is significantly longer than the 134 patients with suboptimal CA19-9 response (39.3 m vs. 21.5 m, p = 0.005) or the 117 SF patients (39.3 m vs. 19.5 m, p < 0.001). Notably, a suboptimal CA19-9 response conferred no OS advantage compared to SF patients. The accumulative incidence of liver metastases (but not other metastases) was significantly reduced only in patients with optimal CA19-9 response to NAC (multivariable-adjusted subdistribution HR = 0.26, p = 0.03). ConclusionCA19-9 response to NAC may serve as the marker for effective NAC. These findings warrant validation in a multi-institutional study.

Relevance of adjuvant chemotherapy in elderly patients with low rectal tumors.

37 Background: The balance between the benefits and toxicities of adjuvant systemic chemotherapy is crucial in the elderly, and often co-morbid patients who have undergone total mesorectal excision (TME) surgery for carcinomas of the lower rectum (1). Tumour distance from the anal verge is a known prognostic factor in rectal cancer (2, 3) and it may influence the effectiveness of adjuvant chemotherapy (AC) (4). This study evaluated the differences in the survival outcomes between patients on surveillance(S) and those who received AC in a multi-centre, real-world setting with a focus on the elderly cohort. Methods: Data was extracted from electronic patient records from 4 NHS trusts in Kent, UK. We retrospectively analysed records of patients between 1 Jan 2014 and 31 Dec 2019, who had neoadjuvant chemoradiotherapy, were down-staged and then offered either S or AC based on clinician’s judgement. The tumour distance from the anal verge was measured through high resolution MRI. The patients were downstaged following assessment as their pTNM staging was lower than their cTNM staging. Results: 589 patients treated for rectal cancer were identified. Of these, 168/589(28%) had non-metastatic disease, were later down-staged at TME and were offered S or AC. 95/168 (57%) of these patients received AC. Patients who received AC were younger (median age 63 vs 70 years, p&lt; 0.001) and with additional poor prognostic factors such as extramural venous invasion EMVI+ (74 vs 39%, p= 0.001), circumferential resection margin CRM+ (89 vs 70% p = 0.001) and pathological nodal involvement (AJCC stage III disease) ( p&lt; 0.001) (table) compared to those on S. Our findings did suggest that patients on surveillance with tumours &lt; 5cm from the anal verge had a longer disease-free survival(DFS) than those who received chemotherapy; this was especially the case in the elderly patient cohort (HR 0.13 95% CI 0.02-0.99, p= 0.049).Our findings also showed that the DFS benefit for patients under surveillance increased with age. Surveillance was most effective in patients over 60 years old compared to those under 60. However, age or distance from anal verge did not have an impact on overall survival (HR 1.01 95% Cl 0.95-1.08 p= 0.70). Conclusions: Although patients treated with AC were younger than patients on S, their tumours had additional poor prognostic factors. Patients on surveillance with tumours &lt;5cm from the anal verge enjoyed a longer DFS but no OS benefit. Elderly patients with tumours &lt; 5cm from the anal verge with no poor prognostic features could derive a benefit from surveillance and avoid chemotherapy-related toxicity. However, our findings will need to be corroborated in prospective studies. [Table: see text]

Updated results from ALTER-C001 study: Efficacy and safety of anlotinib plus XELOX regimen as first-line treatment followed by maintenance monotherapy of anlotinib for patients with mCRC.

137 Background: The standard first-line therapy followed by maintenance treatment is an optional approach to balance the efficacy and toxicity for metastatic colorectal cancer (mCRC). In general, this approach had been seen PFS benefit in some trials, but probably lack of OS benefit, which indicating that new regimens needed to be explored. Anlotinib, a novel multi-targeted TKI, significantly prolonged the PFS of refractory mCRC in a phase III clinical trial (NCT02332499). Previous results of this study exhibited antitumor efficacy and manageable toxicity for mCRC. Here we report an update results with a longer follow up. Methods: 29 patients with unresectable mCRC, aged 18-75, without prior systemic treatment and ECOG performance status 0-1 would be prospectively included. Anlotinib 10mg and capecitabine 1000mg/m2 was given orally for 14 days in 3-week cycles; oxaliplatin 130mg/m2 was given by intravenous infusion on day 1 in 3-week cycles. After 6 cycles of induction therapy, patients would receive anlotinib (12mg, po, d1~14, q3w) until disease progression or intolerable adverse events. The primary endpoint was PFS. Secondary endpoints included ORR, DCR, DOR and safety. Results: At data cut-off date (June 30, 2022), a total of 31 patients were enrolled, the median age was 57 years, 23 (74%) were males, ECOG PS 0/1 was 18 (58%)/13 (42%), 28 (90%) had more than one metastatic tumor. Among them, 24 patients were available for efficacy assessment. The median PFS was 8.28 months (95% CI: 6.29-10.27) and the median DOR was 6.01 months (95% CI: 4.59-7.43). The ORR was 62.5% (95% CI: 40.6-81.2) and DCR was 91.7% (95% CI: 73.0-99.0) in best overall response assessment, of which the longest duration of treatment was 17.5 months. The treatment-related adverse events (TRAEs) occurred in 31 pts (100.0%) including nausea (58.1%), vomiting (51.6%), neutropenia (51.6%), leukopenia (35.5%), hypertension (35.5%). The Grade 3/4 TRAEs were neutropenia (12.9%), hypertension (12.9%), lipase elevated (9.7%), hypertriglyceridemia (6.5%), and leukopenia (3.2%). Conclusions: The updated results suggested that anlotinib combined with XELOX as first line regimen followed by anlotinib monotherapy as maintenance therapy showed a promising clinical benefit and favorable safety profile for mCRC, and the results needed to be confirmed in trials continued subsequently. Clinical trial information: ChiCTR1900028417 .

Comparative Survival Outcomes of Hyperthermic Intraperitoneal Chemotherapy, Intraperitoneal Chemotherapy and Intravenous Chemotherapy for Primary Advanced Ovarian Cancer: A Network Meta-Analysis.

We aimed to compare the survival outcomes and adverse events of hyperthermic intraperitoneal chemotherapy (HIPEC), intraperitoneal chemotherapy (IP)and intravenous chemotherapy (IP)for primary advanced ovarian cancer. PubMed, CENTRAL (Cochrane Central Registry of Controlled Trials), Embase, Web of Science and Scopus were searched using multiple terms for primary advanced ovarian cancer, including randomized controlled trials and comparative studies in both Chinese and English (up to date 15 August 2022). Outcomes include overall survival, progression-free survival and adverse events. The data were pooled and reported as hazard ratio (HRs) with 95% confidence intervals. The Newcastle-Ottawa Scales were used to assess the risk of bias in the included comparative study. The Cochrane Collaboration's Risk of Bias Tool was used for randomized controlled trials. In total, 32 studies, including 6347 patients and 8 different platinum-based chemotherapy regimens, were included in this network meta-analysis. Our analysis results showed that HIPEC2 (carboplatin with area under the curve 10) exhibited a statistically significant OS benefit compared to IV, weekly dose-dense chemotherapy and HIPEC1 (cisplatin with 75/100 mg/m2). Intraperitoneal plus intravenous chemotherapy was associated with a statistically significantly better likelihood of overall survival compared to IV. For progression-free survival, our statistical results only suggest a better progression-free survival in ovarian cancer patients treated with HIPEC1 compared with weekly dose-dense chemotherapy. No evidence of difference was observed between the other comparison groups. Compared with the non-HIPEC group, HIPEC may had a higher incidence of electrolyte disturbances (≥grade 3). Our statistical analysis suggests that the groups receiving HIPEC2 had a better OS than the groups receiving IV, weekly dose-dense chemotherapy and HIPEC1. For PFS, our analysis only showed HIPEC1 is better than IV. Moreover, HIPEC may lead to a higher incidence of electrolyte disturbances (≥grade 3). HIPEC therapy for advanced ovarian cancer is currently controversial.

Clinical Outcome and Treatment Sequences of Patients with Advanced Pancreatic Cancer Treated with Contemporary Chemotherapy Protocols

Introduction: Systemic therapy is firmly established in patients with advanced or metastatic pancreatic ductal adenocarcinoma (PDAC). Clinical efficacy is still modest and options are limited. Combination therapy protocols such as FOLFIRINOX and gemcitabine/nab-paclitaxel (Gem/NP) define standard-of-care. Patients may receive a sequence of both regimens as first- and second-line palliative treatment. However, there is no guidance regarding a preferred order. Methods: This is a retrospective analysis of clinical characteristics, treatment trajectories, and outcomes of patients with advanced PDAC treated at the West German Cancer Center Essen from 2014 to 2020 to inform treatment decisions with respect to predictive factors, impact of chemotherapy regimen sequence, and maintenance treatment. Results: We identified 170 patients with available follow-up. Of those, 160 (94.1%) patients received palliative CTX for primary metastatic, locally advanced, or recurrent PDAC. Median progression-free survival (PFS) upon first palliative chemotherapy was 4.1 (3.1–5.9) months. First-line FOLFIRINOX was associated with superior PFS (median 6.3 months) and OS (9.7 months, HR 0.7, p = 0.03) as compared to Gem/NP or other regimens (PFS 3.0, OS 6.9 months). However, OS benefit of first-line FOLFIRINOX was lost in patients who received at least two treatment lines (median OS 12.1 vs. 13.1 months, p = 0.43). A landmark analysis of patients with clinical benefit (defined as CR/PR/SD for at least 20 weeks) upon first-line therapy revealed improved OS (HR 0.53, p = 0.02) for patients receiving continued deescalated maintenance therapy. Second-line regimens resulted in similar PFS (overall log-rank p = 0.92, median PFS upon second-line therapy 2.3 [1.8–2.9], per-regimen median between 1.8 and 3.9 months). A previously established systemic inflammation score proved to be strongly prognostic and allowed identification of a patient subgroup with dismal prognosis (OS 2.9 vs. 11.4 months, HR 5.23, p < 0.001), independent of other prognostic factors and with no relevant interaction with the choice of first-line regimen. Conclusion: In this real-world population of PDAC patients treated with contemporary combination chemotherapies, a positive impact of first-line FOLFIRINOX was only observed when no second or further line treatment was administered. Intensity-reduced maintenance therapy may lead to superior survival.

Review of outcomes of combination therapy using yttrium 90 radioembolization and sorafenib/nivolumab for HCC with hepatic vein or IVC invasion

Background A systematic review of the outcomes of combination therapy using Yttrium 90 radioembolization (Y90) and sorafenib/nivolumab for patients with hepatocellular carcinoma (HCC), with hepatic vein (HV) or inferior vena cava (IVC) invasion. The aim of this study is to summarise the results of different studies that used the combination therapy for HCC patients with tumor thrombosis involving the HV or IVC. Method A literature search was performed using keywords in Medline and Google Scholar limited to publications from 2010 to 2021. There were 173 articles identified during the initial literature search. During abstract screening, 81 articles were excluded. Another 83 did not contain information on hepatic vein or IVC invasion. Therefore, 9 articles met the eligibility criteria and were included in the synthesis. Results In total, 37 patients with hepatic vein or IVC invasion were identified. There were 31 patients who were given sorafenib, 7 were given nivolumab and 1 was given both sorafenib and nivolumab. Among the 37 patients, 21 had hepatic vein invasion, 22 had IVC invasion and 6 had both HV and IVC invasion. The median OS was 20.55 months and median PFS was 8.18 months. For the results, 23 patients were evaluated via modified RECIST (mRECIST) criteria and 14 were evaluated via RECIST 1.1. Conclusion The combination of local and systemic therapies demonstrated potential results for increased response rates, OS and PFS benefits. Further studies are required to determine the long-term outcomes of the combination therapy for this group of patients.