bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nivolumab (NIVO) plus chemotherapy (chemo) vs chemo as first-line (1L) treatment for advanced gastric cancer/gastroesophageal junction cancer/esophageal adenocarcinoma (GC/GEJC/EAC): 3-year follow-up from CheckMate 649.
Authors: Janjigian Yelena Y. , Shitara Kohei , Moehler Markus H. , Garrido Marcelo , Gallardo Carlos , Shen Lin , Yamaguchi Kensei , Wyrwicz Lucjan , Skoczylas Tomasz , Campos Bragagnoli Arinilda Silva , Liu Tianshu , Tehfe Mustapha , Elimova Elena , Bruges Maya Ricardo Elias , Cleary James M. , Karamouzis Michalis , Soleymani Samira , Lei Ming , Amaya-Chanaga Carlos , Ajani Jaffer A. 
Published: June 2023

4025 Background: NIVO + chemo demonstrated superior overall survival (OS) and clinically meaningful progression-free survival (PFS) benefit vs chemo and acceptable safety in previously untreated patients (pts) with advanced GC/GEJC/EAC, leading to approvals in multiple countries including the US. NIVO + chemo continued to demonstrate clinically meaningful improvement in efficacy after 2 years of follow-up. We present efficacy and safety analyses from NIVO + chemo vs chemo from the 3-year follow-up of CheckMate 649. Methods: Adults with previously untreated, unresectable advanced, or metastatic GC/GEJC/EAC were enrolled, regardless of programmed death ligand 1 (PD-L1) expression, excluding pts with known HER2-positive status. Pts were randomized to NIVO (360 mg Q3W or 240 mg Q2W) + chemo (XELOX Q3W or FOLFOX Q2W), NIVO + ipilimumab, or chemo. Primary endpoints for NIVO + chemo vs chemo were OS and PFS by blinded independent central review (BICR) in pts with PD-L1 combined positive score (CPS) ≥ 5. Results: 1581 pts were concurrently randomized to NIVO + chemo or chemo. With 36-month (mo) minimum follow-up, NIVO + chemo continued to demonstrate OS and PFS benefit vs chemo in pts with PD-L1 CPS ≥ 5 and all randomized pts. The objective response rate (ORR) per BICR in pts with PD-L1 CPS ≥ 5 who had measurable lesions at baseline was 60% (95% CI 55–65) with NIVO + chemo vs 45% (95% CI 40–50) with chemo; in all randomized pts, ORR per BICR was 58% (95% CI 54–62) with NIVO + chemo vs 46% (95% CI 42–50) with chemo. Responses were more durable with NIVO + chemo vs chemo in pts with PD-L1 CPS ≥ 5 (median [m] duration of response [mDOR] 9.6 mo [95% CI 8.2–12.4] vs 7.0 mo [95% CI 5.6–7.9], respectively) and in all randomized pts (mDOR 8.5 mo [95% CI 7.7–9.9] vs 6.9 mo [95% CI 5.8–7.2], respectively). OS benefit with NIVO + chemo was observed across most prespecified subgroups. No new safety signals were identified. A summary of treatment-related adverse events (TRAEs) is shown in the Table. Additional analyses will be presented. Conclusions: After 3 years of follow-up, NIVO + chemo continued to demonstrate clinically meaningful long-term survival benefit with acceptable safety, further supporting its use as a standard 1L treatment in previously untreated pts with advanced GC/GEJC/EAC. Clinical trial information: NCT02872116 . [Table: see text]
Final survival results of ipilimumab or FOLFOX in combination with nivolumab and trastuzumab in previously untreated HER2 positive esophago gastric adenocarcinoma: The randomized AIO INTEGA trial.
Authors: Tintelnot Joseph , Stein Alexander , Paschold Lisa , Goekkurt Eray , Schultheiß Christoph , Thuss-Patience Peter C. , Lorenzen Sylvie , Ettrich Thomas Jens , Riera Knorrenschild Jorge , Jacobasch Lutz , Kubicka Stefan , Al-Batran Salah-Eddin , Reinacher-Schick Anke C. , Pink Daniel , Sinn Marianne , Lindig Udo , Hinke Axel , Hegewisch-Becker Susanna , Binder Mascha 
Published: June 2023

4026 Background: In metastatic esophagogastric adenocarcinoma (EGA), the addition of PD-1 inhibitors (i) to chemotherapy has improved the outcome in selected patient populations. The randomized INTEGA trial investigated trastuzumab and PD-1i with FOLFOX or CTLA-4i in 1st line treatment of advanced HER2+ EGA. Methods: Patients with previously untreated, metastatic HER2+ (local IHC3+ or 2+/ISH+) EGA, and adequate organ function were randomized to trastuzumab and nivolumab (1mg/kg Q3W x4 /240mg Q2W for up to 12 months) in combination with ipilimumab (3mg/kg x4 Q3W; Ipi arm) or mFOLFOX6 (FOLFOX arm) accompanied by a large translational program. The primary endpoint was the 12month overall survival (OS) rate. The trial was registered at ClinicalTrials.gov, NCT03409848. Results: Between March 2018 and May 2020, 97 patients were enrolled and 88 randomized across 21 German sites with the following baseline characteristics: female/male 18/70, median age 60.5 (range 41-80), ECOG 0/1 54/34, GEJ/stomach 66/22. Central post hoc biomarker analysis on 82 evaluable patients showed PD-L1 CPS≥1/≥5 in 59/46 patients and confirmed HER2 (central IHC3+ or 2+/ISH+) positivity in 77 patients. The observed OS rate at 12 months was 70% (95% confidence interval (CI) 54-81%) in the FOLFOX arm, and 57% (95% CI 41-71%) in the Ipi arm. The progression free survival was 10.7 and 3.2 months, and the overall response rate was 53.5% and 34% in the FOLFOX and the Ipi arm, respectively. Although these data are in favor of the FOLFOX arm, the overall survival curves crossed with increased follow-up (median follow-up of 18.8 months) and thus the final median OS was 22.1 and 23.3 months, numerically favoring the Ipi arm. According to the centrally assessed CPS the OS was: 22.1 and 32.2 months in the CPS<5 group, and 22.7 and 12.6 months in the CPS≥5 group for the FOLFOX and the Ipi arm, respectively. Notably, the median tumor burden calculated as the sum of target lesions was numerically lowest in the Ipi arm with higher than median OS. Conclusions: In contrast to limited short term efficacy of the Ipi arm as reflected by the lower PFS, the Ipi arm showed favorable OS, that was inversely correlated to the CPS status. Further analysis of baseline clinical and molecular data to better identify the subgroup of patients benefitting the most of trastuzumab/nivolumab/ipilimumab will be presented at the meeting. Clinical trial information: NCT03409848 . [Table: see text]
Effect of autologous lymphocytes combined with chemotherapy as the first-line treatment of advanced gastric cancer.
Authors: Ma Xiaoting , Yang Lin 
Published: June 2023

4037 Background: To evaluate the safety and initial efficacy of adoptive cell therapy (ACT) combined with SOX in first-line treatment of locally advanced unresectable or metastatic gastric adenocarcinoma/gastroesophageal adenocarcinoma. Methods: In this single-arm, single-center exploratory trial, patients with histologically confirmed locally advanced unresectable or metastatic gastric adenocarcinoma/gastroesophageal adenocarcinoma were randomly assigned (1:1) to receive ACT in combination with S-1 and oxaliplatin (SOX) or SOX alone. The primary endpoint was the incidence of adverse events (AEs). Secondary endpoints were progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and disease control rate (DCR). Results: Fifty-nine patients were enrolled in the study between November 20, 2014 and September 6, 2017. 31 patients received ACT combined with SOX (ACT-SOX) and 28 patients received SOX. The most common AEs in both groups were gastrointestinal reaction, leucopenia, neutropenia, anemia, thrombocytopenia, hyperbilirubinemia and elevated aspartate transaminase concentration, with a higher incidence in the SOX group. The median PFS for ACT-SOX and SOX were 6.9 and 4.9 months respectively (HR 0.80, p=0.45), and the median OS were 17.8 and 9.75 months (HR 0.76, p=0.34). Patients who received more than three injections of specific lymphocyte subsets benefited the most from combination therapy. Cox univariate and multivariate analysis showed that tumor metastasis to more than two organs was the main risk factor for PFS and OS. 29 patients in the ACT-SOX group and 25 in the SOX group had measurable lesions. The ORR of ACT-SOX group and SOX group was 55.2% and 32.0%, and DCR of two groups was 93.1% and 88.0%. Conclusions: The safety of ACT-SOX in first-line treatment of patients with locally advanced unresectable or metastatic gastric adenocarcinoma/gastroesophageal adenocarcinoma is good. Compared with SOX alone, although the PFS and OS of ACT-SOX did not reach statistical difference, it could further extend the time of PFS and OS, and the absolute improvement time of OS was about 8.05 months. Continuous benefit of ACT-SOX was observed through long-term follow-up. Clinical trial information: NCT02504229 .
Health-related quality of life (HRQOL) in patients (pts) with advanced gastric cancer/gastroesophageal junction cancer (GC/GEJC) or esophageal adenocarcinoma (EAC): 36-month results of nivolumab plus chemotherapy (N+C) versus (C) from CheckMate 649.
Authors: Elimova Elena , Wyrwicz Lucjan , Chen Clara , Blum Steven Michael , Davenport Eric , Wang Jinyi , Kondo Kaoru , Moehler Markus H. 
Published: June 2023

4038 Background: CheckMate 649 (NCT02872116) is a randomized, open-label, phase 3 study in first-line treatment of pts with advanced GC/GEJC/EAC. Primary results showed statistically significant improvement in overall survival (OS) for N+C versus C in all randomized pts. Prior analyses conducted for 24-month follow-up (FUP) showed pts receiving N+C maintained HRQOL and experienced delayed deterioration in HRQOL compared with pts receiving C. Here we report additional analyses of HRQOL with 36-month FUP data. Methods: Functional Assessment of Cancer Therapy–Gastric Cancer (FACT-Ga) and EQ-5D-3L results were collected at baseline (BL) and every 6 weeks while on treatment. Change from BL in FACT-Ga, EQ-5D Visual Analog Scale (VAS), and Utility Index (UI) scores were analyzed using mixed models. Time to first symptom deterioration (TTSD), time until definitive deterioration (TuDD), and time to improvement (TTI) were estimated with Kaplan-Meier estimators and stratified Cox models; deterioration/improvement events were based on prespecified meaningful thresholds for change scores. Results: A total of 1,581 pts were randomized to N+C (n = 789) and C (n = 792); of those, 1,360 pts had BL and post-BL PROs and were included in the PRO population (N+C [n = 694] and C [n = 666]). With additional follow-up, least-squares mean differences from BL remained comparable between groups across visits for HRQOL measurements with exceptions. FACT-Ga total score, GaCS, physical well-being (WB), and emotional WB tended to favor N+C; social WB tended to favor C. For all randomized pts, most time-to-event endpoints favored N+C; like the 24-month analysis, statistically significant delays in deterioration were maintained for TuDD (except FACT-G Social WB) and TTSD (only FACT-GaCS and FACT-Ga total). Conclusions: These results confirm the earlier 24-month FUP findings. Compared with C alone, N+C maintained HRQOL with decreased risk of deterioration in pts with previously untreated advanced or metastatic GC/GEJC/EAC. Together with improved OS, data continue to support N+C as a first-line standard treatment for GC/GEJC/EAC. Clinical trial information: NCT02872116 . [Table: see text]
Efficacy of ramucirumab combination chemotherapy as second-line treatment in patients with advanced adenocarcinoma of the stomach or gastroesophageal junction after exposure to checkpoint inhibitors and chemotherapy as first-line therapy within the prospective phase II IKF-S628/AIO-STO-0417 (MOONLIGHT) trial.
Authors: Masetti Michael , Al-Batran Salah-Eddin , Goetze Thorsten Oliver , Thuss-Patience Peter C. , Riera-Knorrenschild Jorge , Goekkurt Eray , Folprecht Gunnar , Ettrich Thomas Jens , Lindig Udo , Luley Kim Barbara , Pink Daniel , Dechow Tobias Nicolaas , Sookthai Disorn , Junge Sabine , Pauligk Claudia , Lorenzen Sylvie 
Published: June 2023

4043 Background: FOLFOX plus nivolumab has become standard of care for first-line therapy of patients (pts) with advanced gastroesophageal cancer (aGEC). The efficacy of 2nd line VEGF-2 inhibition with ramucirumab (Ram) plus chemotherapy after progression to immunochemotherapy remains unclear. Methods: Medical records of consecutive pts with aGEC enrolled in the multi-centre randomized phase II AIO-STO-0417 trial who had tumor progression after 1st line FOLFOX plus nivolumab and ipilimumab were retrospectively analysed. Pts were divided into two groups based on the subsequent 2nd line therapy: Ram plus chemotherapy (ramucirumab group) or chemotherapy alone (control group). Outcomes were compared between both groups in the overall population and in subgroup analysis according to best response (CR/PR) under 1st line therapy and tumor PD-L1 expression. Results: In total, 83 pts (38 Ram group, 45 control group) were included. The most frequent 2nd line therapy in the Ram group was Ram plus paclitaxel (85%). In the overall population, median progression-free survival (PFS) in the Ram group was longerthan in the control group (4.5 vs. 2.9 months). Responders (CR/PR) to 1st line immunochemotherapy who received Ram containing 2nd line therapy (n = 15) showed a clearly prolonged median OS counted from start of 1st line therapy (28.9 vs. 16.5 months), as well as 2nd line OS (9.6 vs. 7.5 months), PFS (5.6 vs. 2.9 months) and DCR (53% vs. 29%) compared to the control group (n = 24). PD-L1 CPS ≥ 1 (status known for77% of pts) was 42% and 44% for the Ram and the control group, respectively. Patients with CPS ≥ 1 in the Ram group (n = 16) showed a trend towards better tumor control (ORR 25% vs. 10%, DCR 44% vs. 30%) and improved survival (total OS 11.5 vs. 8.0 months; 2nd line OS 6.5 vs. 3.9 months; PFS 4.5 vs. 1.6 months) compared to the control group (n = 20). Conclusions: Ramucirumab is effective as 2nd line treatment after progression on 1st line FOLFOX plus dual checkpoint inhibition, especially in patients with initial response and positive PD-L1 expression. Sequential angiogenesis inhibition with anti-VEGFR-2 targeting therapy following immunochemotherapy might be a promising option to overcome resistance to immunotherapy, which warrants further investigations in a larger cohort. Clinical trial information: NCT03647969 .
Heterogeneous baseline immune cell infiltration landscape as a predictor of pathological complete response in locally advanced esophageal squamous cell carcinoma (ESCC) following neoadjuvant chemotherapy and immunotherapy: Results from a single-arm, phase II clinical trial (SEEK-01).
Authors: Yao Guangyu , Wang Renfeng , Huang Zhiliang , Du Chaoxiang , Chen Borong , Lin Zhenyang , Zhang Tao , Wu Zhonghua , Fan Hong 
Published: June 2023

4047 Background: Neoadjuvant immunotherapy and chemotherapy have shown promise in improving outcomes for patients with locally advanced ESCC, but the response to treatment can vary among patients. Therefore, there is a need to identify predictive biomarkers that can guide treatment decisions and improve patient outcomes. The infiltration of immune cells within the tumor microenvironment has been shown to be an important factor in cancer progression and response to treatment. In this study, we sought to explore the immune microenvironment prospectively related to treatment response of Neoadjuvant immunotherapy by scRNAseq. Methods: This was a single-arm phase II clinical trial, planned to enroll 20 locally advanced ESCC patients (cT2-4N0-1M0). After neoadjuvant chemotherapy (paclitaxel-albumin + carboplatin) combined with tislelizumab, patients received minimal invasive esophagectomy (MIE).Prior to neoadjuvant therapy, fresh tumor tissues were obtained via endoscopy and used for scRNAseq analysis, to evaluate the predictive capacity of the immune microenvironment. Pathological outcomes were assessed and divided into pCR, MPR defined as <10% residual tumor excluding pCR, and non-MPR defined as >10%. Results: Out of 18 enrolled patients, 15 completed neoadjuvant therapy and MIE surgery since March 2022. Of these 15 patients, 3 achieved pCR, 2 got MPR, and 10 were non-MPR, with a total of 51,208 single cells sequenced. Both groups showed similarly low expression of PD-L1 (5.7% vs. 2.3%). Comparing pCR to non-MPR patients, the former showed a significant increase in T lymphocytes (CD8+(17.1% vs.1.1%), Regulatory T(20.2% vs.4.0%)), plasma cell(22.0% vs.8.3%), and mature dendritic cell(1.5% vs.0.5%); a significant decrease in B cells(0.9% vs. 1.9%), neutrophils(1.7% vs.11.0%), and tumor cell, as well as a similar expression of macrophage(5.6% vs.6.6%) and monocyte, indicating a clear difference in the immune cell infiltration landscape between two groups. Furthermore, we identified a new subtype of plasma cell which was highly enriched in the non-MPR group, even though the pCR group showed a great increase in plasma cells in total. Conclusions: This study demonstrates the heterogeneity of baseline immune cell infiltration landscape in Locally Advanced ESCC, in which pCR and non-MPR patients exhibited entirely different profiles, and provide a potential predictor of response to neoadjuvant immunotherapy. Our findings suggest that baseline immune cell infiltration status, rather than pd-L1 expression, could accurately predict pCR or non-MPR before treatment, which could guide personalizing and minimize the need for trial-and-error approaches.
Effectiveness and safety of camrelizumab in advanced esophageal cancer: A prospective multicenter observational cohort studies (ESCORT-RWS).
Authors: Lu Zhihao , Zhao Jun , Yang Zhe , Li Na , Wang Junsheng , Yuan Shuanghu , Wang Yusheng , Li Suyi , Ran Fengming , Ji Yinghua , Zhang Yanqiao , Wang Chen , Wan Lixin , Wang Ming , Liang Liang , Dai Xiaofang , Cheng Guanghui , Li Wei , Zhen Peng , Shen Lin 
Published: June 2023

4049 Background: Camrelizumab, an anti-programmed death 1 (PD-1) monoclonal antibody, has demonstrated survival benefits in patients with advanced or metastatic esophageal squamous cell carcinoma. However, the real-world effectiveness and safety of camrelizumab in patients with advanced esophageal cancer are largely unknown. Methods: In this prospective multicenter observational cohort study (NCT04616040), patients with advanced esophageal cancer who were scheduled to receive camrelizumab at the discretion of the physicians in charge were screened for inclusion. Clinical outcomes were treatment emergent adverse events (TEAEs), objective response rate (ORR), disease control rate (DCR), time to treatment discontinuation (TTD), progression free survival (PFS), and overall survival (OS). Results: Between Dec. 24, 2020 and Dec. 30, 2022, data were available for 624 patients (median age: 64.5 years; 74 [11.9%] aged ≥75 years; 515 [82.5%] men; 20 [3.2%] ECOG PS ≥2; 602 [96.5%] esophageal squamous cell carcinoma) from 42 institutions in China. All patients received at least one dose of camrelizumab-containing therapy, including 305 (48.9%) in the first-line, 238 (38.1%) in the second-line, and 81 (13.0%) in the third or later line settings. Most patients were treated with camrelizumab plus chemotherapy (487 [78.0%], primarily taxane and platinum-based chemotherapy in 284 [45.5%] patients), followed by camrelizumab plus antiangiogenic therapy (64 [10.3%]), camrelizumab monotherapy (46 [7.4%]), and camrelizumab plus antiangiogenic therapy and chemotherapy (27 [4.3%]). TEAEs occurred in 541 (86.7%) patients, most commonly anemia (41.2%), decreased white blood cell (38.5%), and decreased neutrophil count (28.5%). No new safety signals were noted. At the data cutoff (Dec. 30, 2022), 152 (24.4%) patients were still on treatment. The median follow-up estimated by the reverse Kaplan-Meier method and effectiveness outcomes are summarized in the Table. Conclusions: The real-world effectiveness and safety profiles of camrelizumab in advanced esophageal cancer patients are generally consistent with those observed in pivotal clinical trials. [Table: see text]
Circulating tumor DNA and association with CAR-T cell therapy response in gastric and pancreatic cancer patients.
Authors: Kubendran Sindhu , Boland Julia L. , Jurdi Adham A , Ween Audrey , Baker Gabriel , Ma Hong , Baffa Raffaele , Li Zonghai , Botta Gregory P. 
Published: June 2023

4053 Background: Circulating tumor DNA (ctDNA) is a form of cell free DNA that can be used to detect and measure cancer molecular residual disease (MRD) before and after systemic therapy. There are no data pertaining to the assessment of MRD in patients with solid tumors treated with chimeric antigen receptor T-cell (CAR-T) therapy. Here, we evaluated a tumor-informed ctDNA assay in the setting of gastric and pancreatic malignancies treated with claudin18.2 (CT041)-targeted CAR-T cell therapy (NCT04404595). Methods: A single-center review between 7/1/2021 – 1/1/2023 identified 10 patients with pancreatic or gastric carcinoma who received CAR-T CT041 cell therapy. Eight patients were ctDNA positive prior to treatment and had blood samples serially drawn before and after CAR-T cell therapy. Banked plasma was analyzed for ctDNA using a tumor-informed Signatera, mPCR-NGS ctDNA assay (Natera, Inc.). The correlative prognostic value of ctDNA to predict response after CAR-T cell therapy was analyzed by RECIST 1.1 criteria. Results: Pre- and post-treatment serial ctDNA was available for 8 of 10 (3/5 gastric and 5/5 pancreatic cancer) patients and all 8 were ctDNA positive prior to CAR-T CT041 cell therapy. The median nadir of ctDNA was on day 14 after CT041 infusion.Of the 8 patients with detectable ctDNA, 5 (62.5%) became undetectable at some time after CT041 therapy, while 3 (37.5%)remained ctDNA positive throughout treatment. The disease control rate (DCR) was 80% for anytime negative ctDNA patients (4/5). Of patients with responsive disease after CT041 CAR-T, 2/3 (67%) achieved undetectable ctDNA and 1/3 (33%) had a ctDNA reduction by 95%. Both patients with stable disease developed undetectable ctDNA. In those patients with progressive disease, 1/3 (33%) had a negative anytime ctDNA. One patient with a complete response had undetectable ctDNA and target lesion response, then later developed progressive disease detectable by ctDNA 3 months prior to radiography. Overall survival was higher (9.1 months vs. 3.7 months) in those who achieved anytime undetectable ctDNA. Conclusions: Tumor-informed ctDNA correlates with response to CAR-T cell therapy in gastrointestinal malignancies. Ongoing clinical trials of CT041 CAR-T cell therapy will continue ctDNA analysis prospectively. Characteristics of initially ctDNA positive patients receiving CAR-T therapy. Clinical trial information: NCT04404595 . [Table: see text]