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Interim safety and efficacy data of [ ²¹² Pb]VMT-α-NET in somatostatin receptor 2 (SSTR2) expressing neuroendocrine tumors (NETs).

668 Background: After the approval of 177Lu DOTATATE, a new generation of radiopharmaceutical therapies (RPT) utilizing alpha-emitting radiometals is being developed as front-line therapies for advanced NETs with the hope of higher clinical efficacy. In this Phase I study, [ 212 Pb]VMT-α-NET, a novel targeted alpha radionuclide therapy (TAT) to SSTR2, is being evaluated in SSTR2-expressing NETs tumors in patients with no prior PRRT treatment. Here we present interim safety and the first efficacy results from dose escalation cohorts 1 and 2. Methods: In this first-in-human dose-escalation study, safety, PK, and efficacy of [ 212 Pb]VMT-α-NET were investigated in a population of well-differentiated adult NETs of any grade which progressed after prior standard of care therapy as assessed by RECIST v1.1 (NCT05636618). No patient may have received prior 177 Lu-DOTATATE or PRRT. The dose escalation design includes four cohorts, 3 mCi, 5 mCi, 7.5 mCi and 10 mCi based on a Bayesian modified toxicity probability interval (mTPI-2) design. Subjects in cohorts 1 and 2 underwent dosimetry evaluations using the therapeutic surrogate [ 203 Pb]VMT-a-NET. Therapeutic [ 212 Pb]VMT-a-NET was administered for 4 cycles Q8W in combination with reno-protective amino acids. The DLT assessment period is defined as the first 6 weeks of cycle 1. The primary objectives include the evaluation of safety and tolerability, the PK and RP2D of [ 212 Pb]VMT-a-NET as well as ORR as assessed by RECIST 1.1 criteria. Results: The current data cut occurred on September 19 th , 2024. A total of 9 patients were enrolled (2 in cohort 1 and 7 in cohort 2). Median exposure for cohort 1 was 2.5 mCi (2.5 mCi, 2.5 mCi) and for cohort 2 was 5.1 mCi (4.7 mCi, 5.2 mCi). No DLTs were observed. Two grade 3 AEs occurred in Cohort 2 (diarrhea, syncope). The most frequent related TEAE were alopecia, fatigue, anemia, lymphopenia and nausea (all grade 1 or 2). One subject in Cohort 2 was discontinued due to progressive disease. Landmark PFS at 9 months is 89%. ORR is not yet mature and will be shown at the time of the meeting. Safety Monitoring Committee (SMC) meeting was held on July 17 th , 2024, recommended dose escalation to cohort 3 at 7.5 mCi. No nephrotoxicity was reported in either cohort. Conclusions: [ 212 Pb]VMT-α-NET is safe up to 185 MBq (5 mCi) dose level, and the SMC supported dose escalate to cohort 3 at 277.5 MBq (7.5 mCi) following a mandated FDA review in fall. Cohort 2 remains open for dose level expansion. Early efficacy results demonstrate encouraging progression-free survival. Clinical trial information: NCT05636618 .

Pairing up with GLP-1 to combat obesity

Me vs. the machine? Subjective evaluations of human- and AI-generated advice

Abstract Artificial intelligence (“AI”) has the potential to vastly improve human decision-making. In line with this, researchers have increasingly sought to understand how people view AI, often documenting skepticism and even outright aversion to these tools. In the present research, we complement these findings by documenting the performance of LLMs in the personal advice domain. In addition, we shift the focus in a new direction—exploring how interacting with AI tools, specifically large language models, impacts the user’s view of themselves. In five preregistered experiments (N = 1,722), we explore evaluations of human- and ChatGPT-generated advice along three dimensions: quality, effectiveness, and authenticity. We find that ChatGPT produces superior advice relative to the average online participant even in a domain in which people strongly prefer human-generated advice (dating and relationships). We also document a bias against ChatGPT-generated advice which is present only when participants are aware the advice was generated by ChatGPT. Novel to the present investigation, we then explore how interacting with these tools impacts self-evaluations. We manipulate the order in which people interact with these tools relative to self-generation and find that generating advice before interacting with ChatGPT advice boosts the quality ratings of the ChatGPT advice. At the same time, interacting with ChatGPT-generated advice before self-generating advice decreases self-ratings of authenticity. Taken together, we document a bias towards AI in the context of personal advice. Further, we identify an important externality in the use of these tools—they can invoke social comparisons of me vs. the machine.

Metabolic dysfunction in mice with adipocyte-specific ablation of the adenosine A2A receptor

Bifunctional anti-PD-L1/TGF-βRII agent SHR-1701 plus chemotherapy as first-line treatment for advanced esophageal squamous cell carcinoma (ESCC): Survival results of a phase II trial.

411 Background: Recently, several clinical trials have demonstrated synergistic efficacy by combining immune checkpoint inhibitors (ICIs) with chemotherapy. However, only a subset of patients (pts) derived benefits. Combining ICIs with agents blocking immunosuppressive pathway may expand the clinical benefit of ICIs to more pts. Transforming growth factor β (TGF-β) participates in tumor immune escape. SHR-1701, a novel bifunctional fusion protein consisting of a monoclonal antibody targeting PD-L1 fused with the extracellular domain of TGF-β receptor II, was evaluated in a phase II trial (ChiCTR2000039909) to assess its efficacy and safety when combined with chemotherapy for pts with unresectable locally advanced, recurrent or metastatic ESCC in China. Methods: This trial enrolled treatment-naive pts with histologically or cytologically confirmed unresectable locally advanced, recurrent, or metastatic ESCC. Eligible pts received SHR-1701 (30mg/kg, iv, d1, q3w) in combination with up to six cycles of albumin-bound paclitaxel (125mg/m 2 , iv, d1, d8, q3w) and cisplatin (75mg/m 2 , iv, d1, q3w). For those without progressive disease, maintenance treatment was administered with SHR-1701 monotherapy until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), disease control rate (DCR) and safety. Results: At the data cut-off, March 1, 2024, 24 pts had received at least one dose of the study treatment and were included in both the intention-to-treat (ITT) analysis and safety analysis sets. 3 and 12 pts achieved confirmed complete and partial responses, respectively. The confirmed ORR was 62.5% and DCR was 87.5%. With a median follow-up of 20.8 months (95% CI, 15.5-NR), the median duration of response was 9.1 months (95% CI, 6.9-NR). The median PFS was 10.8 months (95% CI, 7.8-NR) and the median OS was 26.1 months (95% CI, 8.6-NR). 12-month PFS and OS rates were 41.4% (95% CI, 22.5-76) and 64.8% (95% CI, 47.8-87.9), respectively. Grade 3-4 treatment-related adverse events occurred in 11 (45.8%) pts and no treatment-related death was observed. Conclusions: The results highlighted that SHR-1701 plus chemotherapy as first-line therapy maintained long-term, durable survival benefit in pts with advanced ESCC. Clinical trial information: ChiCTR2000039909.

Impact of insurance status on mortality following surgical treatment of colorectal cancers.

40 Background: Healthcare disparities in colorectal cancer, driven by insurance status and socioeconomic factors, lead to delayed diagnoses and poorer surgical outcomes. We sought to examine the impact of insurance status on presentation, treatment, and in-hospital mortality in CRC patients undergoing colectomy using the Nationwide Inpatient Sample (NIS) database. Methods: We included patients aged 18-65 years diagnosed with colon cancer and undergoing colectomy, as identified by ICD-9-CM codes, who had private insurance, Medicaid, or no insurance from January 1, 2005, through December 31, 2014. The primary variable was insurance status; patient characteristics such as age, sex, race, income, and tumor type were analyzed. We used the Elixhauser comorbidity index to control for confounding and performed a subset analysis on patients without major comorbidities. The primary outcome was in-hospital postoperative death. Associations between this outcome and insurance status were analyzed using the Cox proportional hazard model, both in the full cohort and in a subset of patients without comorbidities, with models stratified by hospitals to account for clustering effects from variations in access to care. Results: The study cohort included 301,304 patients, of whom 238,158 (79.0%) were privately insured, 40,417 (13.4%) on Medicaid, and 22,729 (7.6%) were uninsured. Most patients were White (71.6%), followed by African American (12.6%), Hispanic (8.4%), Asian/Pacific Islander (3.8%), and Native American (0.5%). A total of 55.4% of cases took place in teaching hospitals. In the unadjusted analysis, the mortality rate for privately insured patients was 0.7% (95% CI, 0.6%-0.7%) compared with 2.1% for uninsured patients (95% CI, 1.7%-2.5%) and 1.5% for Medicaid recipients (95% CI, 1.2%-1.8%; p=0.001). After adjusting for patient characteristics and stratifying by hospital in patients with no comorbidity, uninsured patients still had a higher risk of experiencing in-hospital death (HR, 1.60; 95% CI, 1.24-2.07) compared with privately insured patients, while no significant disparity was found in Medicaid recipients (HR, 0.95; 95% CI, 0.75-1.22) (Table). Conclusions: Uninsured patients undergoing colectomy for colon cancer experienced the highest in-hospital mortality, a disparity not fully explained by overall health differences. These findings underscore the critical role of insurance coverage in improving surgical outcomes and highlight the need for policy interventions to reduce mortality disparities. In-hospital mortality after surgery for colorectal cancer. Covariate Full sample Patients With No Comorbidity Patients With No Comorbidity in Urban Teaching Hospitals Hazard Ratio (95% Cl) Insurance Private Reference Reference Reference Medicaid 0.95 (0.75-1.22) 1.38 (0.91-2.11) 1.66 (0.91-3.02) Uninsured 1.60 (1.24-2.07) 2.12 (1.42-3.15) 2.28 (1.25-4.16)

Multi-target stool DNA test adherence in average-risk African Americans from 2017-2024.

99 Background: Colorectal cancer (CRC) stands as the second most common cause of cancer-related mortality in the United States, while being the third most common cancer in the country. African Americans (AA) are disproportionately affected with CRC (incidence and mortality), yet the disease can be prevented through screening and early detection. Data reveals that only 59% of AA between ages 45-75 were up to date with CRC screening as of 2021. Broad availability of the navigation-supported, at home multi-target stool DNA (mt-sDNA) test may help mitigate barriers to screening adherence in this population. We examined multi-target stool-DNA (mt-sDNA) test adherence rates in a nationally representative AA population. Methods: Using a national claims database of over 165 million individuals linked with Exact Sciences Laboratories data, mt-sDNA orders for AA patients were retrospectively identified from 2016 to 2024. Average CRC risk individuals aged ≥45 years, and new to mt-sDNA, were included in this analysis. Primary outcome of interest was adherence, defined as mt-sDNA kit return rate within 365-days from shipment. Time to test return was examined as the secondary outcome. Demographics were age, sex, ordering provider, residential geography, payor, and outreach preference. Covariates on adherence were examined using logistic regression. Results: Among 434,951 mt-sDNA orders from 2017-2024, the overall adherence rate was 62%, and the average time to test return was 27.6 days. The cohort included higher percentages of women (61.7%), ages 50-64 years (57.8%), located in Southern US (51.4%), and metro areas (90.9%). Most patients were also commercially insured (56.1%) and received their mt-sDNA order from their primary care provider (65.4%). Digital SMS was the most preferred outreach option (47%). Patients ages ≥76 years demonstrated the highest adherence (70.3%), with all age categories near or above 60% (45-49 yrs [59.4%]; 50-64 yrs [60.8%], 65-75 yrs [64.3%]). Across payors, patients with Medicare had the highest adherence rates (66.5%). Across outreach, highest adherence was among those who preferred ‘Digital SMS + Email’ outreach (64.3%). Men were quicker to return their test than women (26.8 days vs 28 days, p<0.001). Those ages ≥76 years and with tests ordered by GIs had the shortest time to test return (21.3 and 22.2 days, respectively). Adjusted analyses revealed multiple factors were associated with increased odds of adherence, including older age (≥76 years; OR=1.54; p<0.001), ‘Digital SMS + Email’ outreach (OR=1.25; p<0.001), rural residence (OR=1.23; p<0.001), and males (OR=1.05; p<0.001). Conclusions: Mt-sDNA adherence was higher for AA patients in this large, national cohort as compared to previously reported overall CRC screening adherence data for this population group. Findings suggest mt-sDNA utilization, with its included patient navigation, may help reduce screening disparities among AA patients.

Durvalumab (DUR) effectiveness in advanced biliary tract cancer (aBTC) patients based on real-world data evidence.

598 Background: Based on TOPAZ-1 trial, Durvalumab (DUR) plus gemcitabine and cisplatin significantly improved overall survival (OS) in advanced biliary tract cancer (aBTC) patients. Real-World data evidence can evaluate the benefit of this combination outside controlled studies comparing patients treated with standard chemotherapy with or without DUR. Methods: Using the TriNetX Global Collaborative Network, a platform that operates globally based on anonymized and aggregated clinical data, a sample of aBTC patients from 128 healthcare organizations (HCOs) who met the initial criteria was selected. 5-year overall survival (OS) was analyzed between these cohorts using a Kaplan-Meier analysis. Hazard Ratio (HR) and its 95% confidence interval (95%CI) were calculated to evaluate the difference between cohorts. Propensity Score Matching (PSM) was used to balance the cohorts based on age, gender, and race mitigating possible cofounding variables. All statistical analyses were conducted utilizing the TriNetX Analytics function in the online research. Results: A total of 1099 patients met the study criteria and were included in our study. 399 received DUR plus chemotherapy and 700 received only chemotherapy. Patients treated with DUR showed a significant better OS compared to patients treated with only chemotherapy, both previous to PSM and before PSM (post-PMS median OS 418 days vs 359 days, HR 0.862, 95%CI 0.759-0.979, p=0.022). Conclusions: This is the largest World-Real Data study exploring the effectiveness of Durvalumab in aBTC patients outside clinical trials, confirming a similar benefit than TOPAZ-1 study.

FDA approves first HER2 × HER3 bispecific antibody

Bone health in newly diagnosed female breast cancer patients in China: a cross-sectional study

Acidic pH of early endosomes governs SARS-CoV-2 transport in host cells

Economic burden of hepatocellular carcinoma recurrence after curative treatment in Spain.

640 Background: The literature on burden of disease studies of hepatocellular carcinoma is scarce. The aim of this analysis was to quantify the economic burden of disease recurrence in very early or early-stage HCC patients who underwent liver resection, ablation or transplantation in Spain. Methods: A decision-tree model was developed to estimate the cost of a recurrence after curative treatment with an initial complete response of very early or early-stage primary HCC tumor over a 5-year time horizon. Clinical parameters were collected by a multidisciplinary group of experts who also validated the assumptions and results of the analysis. According to the Barcelona Clinic Liver Cancer (BCLC) recommendations, patients with recurrent HCC were classified into five HCC stages (0, A, B, C, and D) and allocated to different treatment options. A payer perspective was adopted, so only direct costs (€2024) were considered (local/locoregional treatments costs, drug acquisition and administration costs, adverse events management costs, diagnostic and follow-up costs and end-of-life costs). Sensitivity analyses were performed to assess uncertainty. Results: A total of 1,250 HCC recurrences were estimated in Spain, resulting in a total cost of €32,817,142 in the first year of recurrence management. After 5-years follow-up, an additional €10,1M was estimated, mainly due to patient surveillance (€2,8M) and 228 new recurrences (€5,7M). The average cost of a relapse was €26,253 euros in the first year of recurrence management, rising to €34,342 euros for 5-years follow-up. A hypothetical patient experiencing a second relapse 5 years after their first relapse would incur costs of €58,758. Conclusions: This study is the first in Spain to explore the economic burden of hepatocellular carcinoma. Estimating the cost of recurrence after curative treatment and complete response of a primary HCC tumor is complex and depends on multiple factors, so further studies exploring both efficacy and costs in hepatocellular carcinoma are needed.

A phase 2 study of intravenous pembrolizumab and intratumorally injected autologous dendritic cells (DCs) in refractory colorectal cancer (CRC).

TPS319 Background: Immune checkpoint inhibitors (ICIs) have shown limited benefit in CRC outside the microsatellite instability high (MSI-H) population. Deficient cytotoxic T lymphocyte (CTL) trafficking to the tumor microenvironment (TME) and excess pro-tumorigenic cytokines and immunosuppressive cells may contribute to primary ICI resistance in microsatellite stable (MSS) CRC. Selective enrichment of T cells with specific chemokine receptors may enhance antitumor immunity. Studies highlight the role of IL-12 in improving progression-free survival (PFS) and overall survival (OS) in patients on DC therapies. Our group developed ST-aDC1s, optimized for high production of high levels of IL-12 and CTL-attracting chemokines when injected intratumorally. In preclinical models, ST-aDC1s combined with anti-PD-1/PD-L1 therapy showed therapeutic synergy, suggesting ST-aDC1s as a promising alternative to traditional DC vaccines for inducing CTL entry into tumors. Methods: We designed an open-label, non-randomized, phase 2 study of intratumoral autologous ST-αDC1 combined with pembrolizumab in recurrent/metastatic unresectable MSS CRC. Eligible patients must have prior treatment with, or contraindication to fluoropyrimidine, irinotecan, oxaliplatin, anti-VEGF, and anti-EGFR therapy (if RAS wild type), be anti-PD-1/PD-L1 therapy naïve, have ECOG PS ≤1, and have at least two target lesions, one amendable to biopsy and injection. Leukapheresis will collect monocytes for ST-αDC1 generation. Patients will receive intratumoral ST-αDC1s (6 million) on days 1 and 8 with biopsies, and an optional dose on day 50 before a third pembrolizumab dose. Pembrolizumab 200 mg IV will start on day 8, given every 3 weeks for 4 doses during the study period. Pembrolizumab will continue as conventional care afterwards. CT scans will occur after 2 and 4 doses of pembrolizumab. A safety lead-in cohort will include six patients, with up to 17 patients enrolled. The primary endpoint is objective response rate (ORR) at 12 weeks per RECIST 1.1. Secondary endpoints are safety, PFS, OS, and ORR per iRECIST. Correlative analysis will assess baseline levels and post-treatment changes in infiltrating T cells, CD4/CD8 ratios, FoxP3+ Tregs, and Teff-attracting and Treg-favoring chemokines from biopsy specimens, and immune cell subsets and cytokine levels from peripheral blood. With an expected ORR under 5% for standard treatment, 17 patients are required to show at least a 25% ORR with 81.2% power and a one-sided type I error rate of 0.05. A Simon two-stage Optimal design will enroll 9 patients in stage 1, and if ≥1 response occurs, 8 more patients will be added in stage 2. If ≥3 responses are observed, the treatment will be deemed promising for further study. Clinical trial information: NCT05518032 .

A phase II study of neratinib (Nera) in combination with chemotherapy/trastuzumab/pembrolizumab (C/T/P) in HER2 overexpressing gastroesophageal cancers (GECs).

TPS514 Background: Human epidermal growth factor receptor 2 (HER2) is overexpressed in about 15-20% of GECs and is tested using immunohistochemistry and/or in-situ hybridization. Per 3 rd interim analysis of KN-811 study, addition of P to C/T improved overall response rate (ORR) and overall survival (OS) in patients with HER2 positive tumors. HER2 heterogeneity and activation of other signaling pathways ultimately leading to T resistance limits its potential to have a durable response. Nera is an anilinoqiunoline derivative intracellular oral kinase inhibitor that irreversibly binds to epidermal growth factor receptor (EGFR), HER2 and HER4. In this study, we hypothesize that targeting other oncogenic pathways with Nera may help derive additional therapeutic benefit in HER2 positive GECs when combined with C/T/P. Methods: This is an open-label, single arm, multi-institutional Phase II study of Nera in combination with C/T/P in HER2 overexpressing GECs as 1 st line treatment. The first 6 pts as a lead-in phase will be evaluated for toxicity. If no dose limiting toxicity (DLT), a total of 30 patients (include the first 6pts in the lead-in phase) will be used to evaluate efficacy in the phase II portion. All pts will receive standard dose mFOLFOX/trastuzumab q2w along with pembrolizumab 400 mg q6w. Nera will be dosed at 240 mg daily. In case of DLTs observed with this dose, a dose of 160 mg/day for Nera will be considered. Estimated sample size is 30-36 pts using Simon 2 stage design. Primary endpoint in ORR. The null hypothesis will be rejected if 26 or more responses are observed in 30 patients. Key inclusion criteria include: HER2 positive GECs (as determined by local testing), treatment naïve for stage IV disease, measurable disease, ECOG 0-1, preserved cardiac function. Uncontrolled brain metastases or impaired organ function that poses risk with treatment are key exclusion criteria. Primary endpoint is ORR and secondary endpoints include safety, duration of response, clinical benefit rate and OS. The trial is registered on clinicaltrials.gov under NCT06109467. Clinical trial information: NCT06109467 .

Intra-tumoral CD40 antibody with irreversible electroporation (IRE) in locally advanced pancreas cancer.

TPS787 Background: Irreversible electroporation (IRE) is a form of non-thermal tumor ablation that is currently in clinical use for selected patients with locally advanced pancreatic cancer (LAPC). Preclinical and clinical studies have suggested that IRE generates an in situ vaccination effect by releasing tumor neoantigens in the setting of inflammation. Our published data from syngeneic, orthotopic mouse models demonstrate that combination of IRE with local CD40 agonism induces systemic anti-tumor immune effects, including neoantigen-specific T-cell responses and inhibition of liver metastases (1). Mitazalimab, a second-generation CD40 agonistic IgG1 mAb, has demonstrated promising clinical antitumor activity when delivered systemically in combination with modified FOLFIRINOX in metastatic pancreatic cancer (2). Methods: This clinical trial (NCT06205849) is a phase I dose-escalation study of an agonistic CD40 antibody (mitazalimab) injected intratumorally at the time of surgical IRE in patients with LAPC who have not demonstrated distant disease progression after a minimum of 4 months of optimal standard of care (SOC) chemotherapy (modified FOLFIRINOX). The doses investigated are 25, 75 (starting dose), and 200 µg/kg, in an interval 3+3 design, with a maximum of 18 subjects. The primary endpoints are the rates of dose limiting toxicities (DLTs) and treatment-emergent adverse events (AEs). The secondary endpoints are progression-free survival (PFS) and overall survival (OS). At a liberal alpha of 25%, appropriate for this proof-of-concept early phase study, we have 80% power to detect an improvement in PFS from 12 months (based on prior studies of IRE alone) to 18 months, with an expected 16 evaluable subjects and an anticipated 11 observed events, using a one-sided log-rank test. Candidate neoantigens will be identified by profiling nucleic acids derived from tumor biopsies obtained intraoperatively prior to IRE using our Identification-Prioritization-Validation (IPV) bioinformatic pipeline (3). Blood samples will be collected pre-operatively and 12-weeks post-operatively to evaluate for evidence of neoantigen-specific T-cell reactivity and other neoantigen-independent analyses of immune response. We have enrolled two patients since the study opened in September 2024. 1. J. Shankara Narayanan et al., JITC 2023. 2. J. Van Laethem et al., Lancet Oncol 2024. 3. A. Miller et al., Sci Transl Med. 2024. Clinical trial information: NCT06205849 .

A spatiotemporal distribution prediction model for electric vehicles charging load in transportation power coupled network

Human calpain-3 and its structural plasticity: Dissociation of a homohexamer into dimers on binding titin

A randomized, double-blind, phase III study comparing trifluridine/tipiracil (FTD/TPI) versus placebo in patients with molecular residual disease following curative resection of colorectal cancer (CRC): The ALTAIR study.

LBA22 Background: Tumor-informed circulating tumor (ct) DNA testing is recognized as a powerful predictor of CRC recurrence. However, the benefit of systemic therapy to prevent or delay clinical recurrence in patients (pts) with molecular recurrence after curative surgery remains uncertain. Methods: Pts with CRC who had undergone curative resection of primary and/or metastatic sites + standard of care (SoC) adjuvant treatment if applicable, were enrolled in ALTAIR study if they (1) prospectively tested positive for ctDNA using a clinically validated, personalized assay (Signatera™, Natera, Inc.) within 3 months before enrollment and (2) had no recurrence on radiological (CT) imaging. Pts were randomized to receive FTD/TPI or placebo for 6 months. CT and ctDNA analyses were conducted every 2 months in the first year, every 3 months in the second year, and every 6 months in the third year. The primary endpoint was disease-free survival (DFS), with secondary endpoints including ctDNA clearance, overall survival (OS), and adverse events. The study assumed a median DFS of 8 months in the placebo group, an HR of 0.667 for the FTD/TPI group, 0.05 significance level, 0.80 power, 2-year enrollment, and 1-year follow-up, requiring 240 pts and 190 DFS events. Baseline ctDNA levels were evaluated by mean tumor molecules (MTM)/ml. Results: Between July 2020 and June 2023, 243 pts were enrolled and randomized to FTD/TPI (n=122) or placebo (n=121). Baseline characteristics were balanced, and 96.3% of pts received SoC treatment postoperatively. FTD/TPI group had a median DFS of 9.30 months vs. 5.55 months in the placebo group, but this difference did not reach statistical significance in the primary population (HR, 0.79; 95% CI, 0.60-1.05; P = 0.107). The FTD/TPI benefit was highly significant in resected oligometastatic stage IV pts as shown in Table. The baseline MTM/ml levels were significantly higher in resected oligometastatic Stage IV pts vs non-Stage IV (0.68 vs 0.32, P = 0.024). Overall, FTD/TPI benefit was significantly pronounced with higher MTM/mL, with linear benefit observed with increasing MTM/mL values at the enrollment time point. OS data remain immature, with 24 events reported across both arms. Grade ≥3 adverse events occurred in 73.0% of the FTD/TPI arm versus 3.3% in the placebo arm, with no new safety signals. Conclusions: Although statistical significance was not reached in the primary population, FTD/TPI showed clinically meaningful DFS benefit in pts with resected oligometastatic disease and a trend towards increasing DFS benefits with increasing MTM/mL values. Clinical trial information: NCT04457297 . Number Baseline MTM/ml Median DFS FTD/TPI(months) Placebo (months) Primary population 243 0.40 9.30 5.55 HR, 0.79 P = 0.107 Stage IV 66 0.68 9.76 3.96 HR, 0.53 P = 0.012 Non-Stage IV 177 0.32 9.26 6.05 HR, 0.86 P = 0.378

Bevacizumab plus mFOLFOX6/FOLFIRI sequential bevacizumab plus capecitabine maintenance in RAS-mutated advanced colorectal cancer: A real-world study of first-line/second-line conversion therapy.

77 B ackground: Currently, the standard first-line/second-line treatment for advanced colorectal cancer with RAS mutations is chemotherapy combined with bevacizumab. Patients with colorectal cancer confirmed maintenance therapy can effectively improve progression-free survival, improve patient quality of life. Therefore, this study aims to evaluate the efficacy and safety of bevacizumab combined with mFOLFOX6/FOLFIRI sequential bevacizumab combined with capecitabine as first-line/second-line conversion therapy for RAS-mutated advanced colorectal cancer. M ethods: This is an open-label, single-center study in previously untreated patients with RAS mutant mCRC. Eligible patients received first-line chemotherapy of bevacizumab (5mg/m 2 ) combined with mFOLFOX6/FOLFIRI for 12 cycles randomly, during which the efficacy was assessed every 4 cycles, then followed by bevacizumab(7.5mg/m 2 ) in combination with capecitabine maintenance therapy which assessed every 2 cycles until disease progression, and then switched to the second-line therapy FOLFIRI/mFOLFOX6 combined with bevacizumab which was assessed every 4 cycles until disease progression or intolerable toxicity. Imaging studies were performed to assess treatment efficacy according to RECIST1.1 criteria, and the primary endpoint was progression-free survival (PFS), including first-line PFS and second-line PFS after progression, and the secondary endpoints included disease response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. R esults: This study recruited 78 subjects from January 2021 to May 2024. As of September 10, 2024, a total of 70 subjects were analyzable for the first-line treatment, of which 6 subjects met the surgical criteria after treatment and achieved NED status; 45 patients reached the first-line PFS endpoint, with a median PFS (mPFS) of 249 days (95% CI: 204.4-293.6), an ORR of 38.6%, and a DCR of 95.7% . Twenty patients entered the first-line maintenance therapy, with a mPFS of 358 days (95% CI: 53.8-662.2). For the second-line treatment, a total of 43 subjects were analyzable, of which 35 patients reached the second-line PFS endpoint, with a second-line mPFS of 171 days (95% CI: 89.8-252.1). 41 subjects underwent at least one efficacy evaluation, with ORR of 14.6% and DCR of 75.6%. The most common grade 3 treatment-related adverse events were neutropenia, leukopenia, anemia, hypertension, diarrhea, and thrombocytopenia. There were no treatment-related deaths. No new adverse events occurred during the entire combination treatment period. C onclusions: This real world study has demonstrated good tolerability and encouraging clinical efficacy, especially with potential implications for treatment planning and management strategies for advanced colorectal cancer with RAS mutations. Clinical trial information: ChiCTR2100042553 .

The impact of adherence to NCCN and BCLC treatment guidelines on survival in HCC: A single center study.

561 Background: Hepatocellular carcinoma (HCC) is a prevalent and lethal disease in Saudi Arabia, and globally. Guidelines such as Barcelona Clinic Liver Cancer (BCLC) and National Comprehensive Cancer Network (NCCN) are used to guide therapy for this disease. Adherence to these guidelines should lead to better outcomes. We aim to examine the adherence to guidelines and its impact on survival in a real world setting. Methods: This retrospective cross-sectional study was conducted at the Ministry of National Guard for Health Affairs, Riyadh, Saudi Arabia. Study included all adult patients with HCC who were diagnosed between 2020 and 2023, and presented at our HCC multidisciplinary tumor board (MDT). Data extracted included demographics, clinical and disease characteristics, treatment modalities, and survival status. Chi-square tests, and Kaplan-Meier survival analysis were used to explore relationships between tumor characteristics, adherence to NCCN and BCLC guidelines, and survival outcomes. Adherence to guidelines were assessed by two independent physicians. Results: The study included 208 patients with HCC, the majority were males (73%) with a mean age of 73 years. Less than half of the patients (41.7%) had an Eastern Cooperative Oncology Group (ECOG) performance status of 1. Tumor staging showed that 35% of the patients had BCLC stage D. Child pugh class A and B were equally present in 45% of the patients. Moreover, 24% of the patients had distant metastases or vascular invasion (in portal vein) placing them in BCLC stage C. It is noteworthy that Alpha-Fetoprotein (AFP) was abnormal (>8ng/ml) in 58% of the patients, 18% of them had AFP of more than 400ng/ml. Additionally, the prevalence of comorbid conditions were remarkable for liver cirrhosis being present in 85% of patients, while diabetes mellitus and hypertension each present in 63% of patients. Finally, survival analysis showed a median survival of 16.8 months in all patients with HCC (range 0-47.8 months). Adherence to guidelines were high, with 97.6% (n=203) following NCCN guidelines and 70.7% (n=147) following BCLC guidelines. Following both guidelines showed better survival with mean of 37 months (SD=1.841) in patients with child pugh class A (n=53), and mean survival of 24 months (SD=2.251) in patients with child pugh class B (n=74). Conclusions: Adherence to NCCN guidelines was high in our MDT presented patients compared to BCLC guidelines adherence which was lower, but with comparable survival outcomes.