tbuckley/cabot-search huggingface dataset:
Fruquintinib combined with sintilimab and SOX as conversion therapy for unresectable locally advanced or metastatic gastric/gastroesophageal junction adenocarcinoma (GC/GEJC): A single-arm, open-label, phase 2 clinical trial.
Authors: Fei Ma, Suxia Luo, Bin Zhang, Qi Ma, Sheqing Ji, Zhandong Zhang, Yonglei Zhang, Wei Yang, Liangqun Peng, Dandan Guo, Jinjun Ren, Yuan Zhang, Yueyue Su, Jing Li, Wentao Liu, Jinxi Huang, Weiwei Yuan
Journal: Journal of Clinical Oncology (2024)

e16021 Background: The evidence of conversion therapy for unresectable GC/GEJC is limited. Fruquintinib is an oral, highly selective VEGFR 1/2/3 inhibitor that has synergistic antitumor effects when combined with ICIs/chemotherapy. This study was conducted to evaluate the efficacy and safety of fruquintinib combined with sintilimab and SOX as a conversion therapy in patients (pts) with initially unresectable locally advanced or metastatic GC/GEJC. Methods: Eligible pts received 3 to 6 cycles of fruquintinib (4mg/d, po, qd, d1-14) combined with sintilimab (200mg, iv, d1), oxaliplatin (130 mg/m 2 , iv, d1) and S-1 (40-60mg based on BSA, po, bid, d1-14) every 3 weeks. One more cycle of sintilimab plus SOX was given before resection. Radiographic assessments were performed every 3 cycles and MDTs were employed to determine surgical feasibility. Primary endpoint was R0 resection rate. Secondary endpoints included pathological response, ORR, PFS, OS, and safety. Results: From May 2022 to December 2023, 34 pts (29 males/5 females) with a median age of 62 years (range: 43–76), 71% ECOG PS1, 59% GEJC were enrolled. The unresectable factors included liver metastasis 15% (5/34), peritoneal metastasis 6% (2/34), para-aortic lymph node metastasis 3% (1/34), extensive or bulky lymph nodes 53% (18/34), and local progression 38% (13/34). Five pts had more than one unresectable factors. The ORR and DCR of 29 pts who had at least one preoperative assessment were 65.5% (19 PR) and 96.6%, respectively. Among the 18 pts who had completed surgical conversion, all of them had R0 resection (100%), 2 pts (11.1%) achieved pathological complete response (pCR), and 1 pt reached AJCC-TRG1. The pathological response rate (pRR) according to JCGC (≥ Grade 1b) was 100% (18/18). Additionally, downstaging to pN0 was achieved in 13 pts (72.2%). During preoperative treatment, treatment-emergent adverse events (TEAEs) occurred in 85.3% (29/34) pts, and most events were grade 1–2. Grade 3 TEAEs included 2 cases of neutrophil count decreased, and 1 case of each (platelet count decreased, anemia, diarrhea, and immune-related pneumonitis). No severe surgery-related complication was observed. Conclusions: Fruquintinib combined with sintilimab and SOX as a conversion therapy strategy shown acceptable toxicity in unresectable GC/GEJC and induced very high R0 resection, pathological response, and downstaging rate. The study is ongoing, more data will be disclosed in the future. Clinical trial information: NCT05177068 .
Retrospective study of continued immunotherapy in patients with advanced esophageal squamous cell carcinoma after progression on first-line immunotherapy combination chemotherapy.
Authors: Weiyong Yu, Li Wan
Journal: Journal of Clinical Oncology (2024)

e16025 Background: Immunotherapy combined with chemotherapy has become the standard first-line treatment for advanced esophageal squamous cell carcinoma. However, the disease progression pattern after first-line immunotherapy resistance and the second-line treatment options are not fully understood. This retrospective study was designed to explore the efficacy of continued immunotherapy in advanced esophageal squamous cell carcinoma patients after progression on first-line immunotherapy combination chemotherapy. Methods: We retrospectively analyzed the efficacy of second-line continued immunotherapy in patients with stage IV esophageal squamous cell carcinoma who experienced disease progression after first-line immunotherapy at Huai 'an First People's Hospital from July 2020 to December 2023. The main outcome were progression-free survival (PFS), 3-and 6-month PFS rates, objective response rate (ORR), disease control rate(DCR)and overall survival (OS). Results: A total of 30 eligible patients were included. Median age was 67 years, 20 (66.7%) patients were male. 14 patients achieved partial response (PR), 8 stable disease (SD), illustrating an ORR of 46.7% and a DCR of 73.3%. Median PFS was 3.85 months. In the second-line treatment regimen, 21 (70%) were immunotherapy combined chemotherapy, and the others were immunomonotherapy or combined anti-angiogenic drugs. Conclusions: The current retrospective data shows that a considerable number of patients still could benefit from second-line immunotherapy after the progress of first-line immunotherapy in patients with advanced ESCC. This result brings new hope for the increasingly large population of immune resistance esophageal cancer patients. [Table: see text]
Outcomes of R-MPV followed by ara-c in primary central nervous system lymphoma: A single-center retrospective analysis.
Authors: Aatif Khurshid, Sreshta Paranji, Rohan Kapur, Alec Weber, Michelle Cohen, Rathnamitreyee Vegunta, Karen Seiter, Delong Liu, Tauseef Ahmed, Richard Sweeney, Amir S. Steinberg
Journal: Journal of Clinical Oncology (2024)

e19046 Background: Primary central nervous system lymphoma (PCNSL) lymphoma is a rare non-Hodgkin’s Lymphoma. Currently, there is no uniform consensus in the optimal management of PCNSL. In patients that can tolerate systemic therapy, induction therapy is typically done with a high-dose methotrexate-based regimen, due to evidence of better penetration of the blood brain barrier. One such regimens is high dose methotrexate combined with rituximab, procarbazine, and vincristine (R-MPV). Options for consolidation therapy include high-dose systemic therapy with stem cell rescue (ASCT), whole brain radio therapy (WBRT) and high-dose cytarabine (ara-c) with or without etoposide (EA). At our institution we utilize an R-MPV induction approach with some form of ara-c consolidation without etoposide. We aimed to execute a retrospective cohort study to analyze outcomes of this approach. Methods: All the patients diagnosed with PCNSL who received an induction regimen of R-MPV from 10/01/2020 to 06/01/2023 were included. Data was then gathered by chart review of the electronic medical record. Treatment outcomes were evaluated based on imaging with brain MRIs and PET scans. Central findings such as complete response (CR) rate, progression free survival (PFS) and overall survival (OS) were ascertained. Results: 10 charts were reviewed. 9 out of the 10 patients had a histological presentation consistent with diffuse large B-cell lymphoma; 1 patient had a diagnosis of B-cell lymphoma. In terms of demographics, the patients ages ranged from 54 to 83 years, with a median of 74 years. Complete response was achieved in 5 out of the 10 patients (CR rate of 50%), and no relapse was noted in any of these patients. 2 out of the 10 patients progressed on treatment, with 1 dying from progression of the disease. The median follow-up for patients who were still alive was 24 months. 2-year PFS was 80%, and 2-year OS was 90%. Median PFS and OS were not reached. Mean PFS and OS were 28 months and 30.5 months respectively. Conclusions: Based on our study results, the CR rate we observed for R-MPV appears consistent with existing literature on this regimen and other methotrexate-based induction regimens. Our results for R-MPV with ara-c consolidation provides similar outcomes to existing studies on treatment with different methotrexate-based induction and consolidation with ASCT, particularly the 80% PFS we observed. This percent PFS also appears similar to studies of consolidation with ara-c and EA, and superior to PFS with WBRT. Overall, these results are reassuring as in a specific set of older patients who might not be candidates for ASCT, our specific nonmyeloablative approach could be worthwhile. However, our study does have the limitation of being a single center retrospective perspective. [Table: see text]
First-line TQB2450 plus anlotinib combined with paclitaxel and cisplatin for advanced esophageal squamous cell carcinoma (ESCC): Update results of a multicenter phase II trial.
Authors: Junsheng Wang, Ning Li, Yanzhen Guo, Yufeng Cheng, Baosheng Li, Suxia Luo
Journal: Journal of Clinical Oncology (2024)

e16011 Background: PD-1 inhibitor combined with chemotherapy are the standard first-line treatment for advanced ESCC. Anlotinib, a multitargeted tyrosine kinase inhibitor (TKI), has been demonstrated favorable efficacy and manageable toxicity as both first-line treatment when combined with TP and second-line monotherapy in advanced ESCC. TQB2450 is a novel humanized anti-PD-L1 monoclonal antibody. We conducted a phase II trial to evaluate the efficacy and safety of alotinib combined with TQB2450, cisplatin, and paclitaxel as first-line treatment for advanced ESCC. Here is the update results. Methods: Eligible patients (pts) with previously untreated unresectable locally advanced or metastatic ESCC received TQB2450 (1200mg, iv, d1, q3w) plus anlotinib (10mg, po, d1~14, q3w) combined with paclitaxel (135mg/m 2 , iv, d1, q3w) and cisplatin (60~75mg/m 2 , iv, d1~3, q3w) for 4 - 6 cycles as initial therapy. Patients without progressive disease (PD) continued to receive same dose of anlotinib plus TQB2450 as maintenance therapy until PD or unacceptable toxicity. The primary endpoint was PFS (RECIST version 1.1). Secondary endpoints included iPFS (iRECIST), ORR (RECIST version 1.1), DCR, DOR and safety. Results: At the data cutoff date of November 14, 2023, 50 pts were enrolled with a median age of 64 years (range 41-74), male (39/50, 78%) and ECOG PS 1 (38/50, 76%). Among 43 tumor response evaluable pts , 4 achieved complete response, 32 had partial response and 8 had stable disease. The ORR was 72.00% (95% CI: 57.51, 83.77) and the DCR was 84.0% (95% CI: 70.89, 92.83). The 12-month PFS rate was 66.84% (95% CI: 48.73, 79.79) and the 12-month OS rate was 74.22% (95% CI: 59.06, 84.46), but the median PFS and OS was not reached. The incidence of ≥G3 treatment emergent adverse events was 78%, mainly included neutropenia (44%, 22/50), leukopenia (24%, 12/50) and hypertension (20%, 10/50). 20 pts (48%, 24/50) occurred serious AEs. Conclusions: The combination of TQB2450 plus anlotinib, paclitaxel and cisplatin, demonstrated encouraging efficacy and manageable toxicity in patients with advanced ESCC when used as first-line treatment. Clinical trial information: NCT05013697 .
Immune checkpoint inhibitor retreatment in second-line treatment of esophageal cancer: A real-world study.
Authors: Yixin Kang, Dianbao Zhang, Youjia Mi, Xiedong Niu, Yuan Kang, Dongjie Xie, Wenyao Li, Ce Zhang, Junqiang Yang, Jun Yao
Journal: Journal of Clinical Oncology (2024)

e16034 Background: Immunotherapy combined with chemotherapy has been recommended in several guidelines and consensus for the first-line treatment of advanced esophageal cancer(EC), but it is controversial whether to continue immune checkpoint inhibitors (ICIs) after the progress of first-line immunotherapy. Methods: This was a single-center, retrospective, observational, real-world study to collect general conditions and clinical data of EC patients hospitalized in the First Affiliated Hospital of Henan University of Science and Technology between February 2020 and December 2023. All patients received programmed cell death protein 1 (PD-1) or its ligand (PD-L1) inhibitor combination therapy in the first-line and received at least two cycles of PD-1/PD-L1 inhibitor-based therapy in the second-line setting after progression. We evaluated the efficacy and safety including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), grade 3-5 treatment-related adverse effects (TRAE) and immune-related adverse events (irAEs). We also evaluated the relationship between clinical features and outcomes using univariate and multivariate analyses. Results: We enrolled 214 patients, with a median age 67.9 (47 – 87) years, male sex 66.8%, 201(93.9%) ESCC and 11(5.1%) EAC. In all patients, the mOS and mPFS were 9.6 (95%CI 9.1-10.1) months and 4.4 (95%CI 4.1-4.7) months; The ORR was 33.2%, DCR was 65.9%. 162 (75.7%) patients treated with immunochemotherapy(I+C), 37 (17.3%) patients received immunotherapy combined with anti-angiogenic drugs(I+A) and 15 (7.0%) patients treated with immunotherapy combined with chemotherapy and anti-angiogenic drugs(I+C+A). The mOS were 9.1 (95% CI 8.4 – 9.8) months, 10.0 (95% CI 8.7 – 11.3) months and 11.5 (95% CI 10.7 – 12.3) months, respectively. The mPFS were 4.3m (95%CI 4.0-4.6) months, 4.3 (95%CI 4.0-14.6) months and 6.0 (95%CI 4.2-6.4) months. mPFS and mOS did not have significant difference between these groups. Univariate and multivariate analyses showed that PFS more than 6 months on first-line therapy was an independent prognostic factor for PFS and OS in second-line therapy. The incidence of grade ≥ 3 TRAEs and irAEs were 25.7% and 5.6%. No treatment-related deaths occurred. Conclusions: This real-world data showed PD-1 or PD-L1 inhibitors retreatment might have good efficacy and manageable safety in EC patients who progress after first-line immunochemotherapy. [Table: see text]
Population based assessment of HER-2 and PD-L1 positivity in gastric and gastroesophageal junction adenocarcinomas in a Canadian population.
Authors: Patrick Holland, Rumana Rafiq, Kara Matheson, Kelly Dakin-Hache, Heidi Sapp, Ashley Stueck, Phillip Moss, Myuran Thana, Thomas Arnason, Stephanie Leann Snow
Journal: Journal of Clinical Oncology (2024)

e16038 Background: Current standard of care for advanced gastric and gastroesophageal cancers combines systemic chemotherapy with either human epidermal growth factor receptor 2 (HER-2) or programmed death ligand 1 (PD-L1) targeting therapy. New data is emerging that for patients whose tumours are positive for both HER-2 overexpression and have a PD-L1 combined positive score (CPS) &gt;1%, combining all three treatment modalities results in superior outcomes. There is limited international data, and no Canadian data, exploring the frequency of patients who have tumours that are both HER-2 and PD-L1 positive who will be eligible for this novel treatment approach. Objective: To determine the proportion of patients in Nova Scotia with HER-2 positive gastric and GEJ adenocarcinomas who have a PD-L1 CPS score above established clinical thresholds. Methods: A retrospective review of PD-L1 and HER-2 status for all patients diagnosed with gastric and GEJ adenocarcinomas in Nova Scotia between June 3, 2022 and August 13, 2023 was completed. PD-L1 CPS was evaluated using the 28-8 assay and was considered positive if &gt;1%. HER-2 overexpression was evaluated by immunohistochemistry and in cases with equivocal expression, status was based on fluorescence in situ hybridization. Results: Over the study period, 56 cases of gastric and 42 cases of GEJ adenocarcinoma were identified for a total of 98 cases. The median age of the study population was 73 years (range 38 - 91). 73 patients (74%) were male and 25 patients (26%) were female. HER-2 expression was evaluated in 92 cases, and PD-L1 CPS was evaluated in 95 cases. 19 cases (21%) were HER-2 positive and 86 cases (91%) were PD-L1 positive. 17 HER-2 positive cases were also PD-L1 positive (89%). Conclusions: This study provides population level data in a Canadian context on patients with gastric and GEJ adenocarcinoma with respect to HER-2 overexpression and PD-L1 status. This data will be helpful in planning allocation of clinical and financial resources as a new standard of care for these patients is established.
Real-world evaluation of treatment pattern, time to next treatment (TTNT), healthcare resource utilization (HCRU), and cost of care in follicular lymphoma (FL).
Authors: Sameh R Gaballa, Mei Xue, Po-Ya Chuang, Kaitlyn Esselman, Wesley Furnback, Keri Yang
Journal: Journal of Clinical Oncology (2024)

e19044 Background: FL often becomes relapsed or refractory (R/R) to treatment. This study aimed to analyze TTNT, HCRU, and cost of care in FL. Methods: A retrospective study was conducted using Optum Clinformatics Data Mart to identify patients ≥18 years with ≥1 diagnosis for FL initiating 1L, 2L, 3L, or 4L treatment from 1/2019 to 02/2023. Patients were required to be continuously enrolled for 30 days pre- and post-index date, defined as the date of treatment initiation. Patients were categorized into mutually exclusive cohorts based on treatment regimen. TTNT was measured for patients who had a subsequent treatment within the study period. Total cost of care included both plan- and patient-paid claims, adjusted for inflation (2023 USD). HCRU included outpatient visits and inpatient admissions. Costs and HCRU were reported per patient per month over the treatment duration. Results: There were 4,525 patients initiating 1L treatment and 1,053, 304, and 97 patients initiating 2L, 3L, and 4L treatment, respectively. Median follow-up was 487 days (1L), 430 days (2L), 357 days (3L), and 276 days (4L). The mean age at the index was similar across cohorts (range: 69.6 [1L] to 71.9 [4L]). Rituximab monotherapy (R-mono) was the most utilized treatment in 1L and 2L, followed by bendamustine + rituximab (BR) and R-CHOP (Table). Lenalidomide + rituximab (R2) was the most utilized regimen in 3L and 4L. Obinutuzumab monotherapy (O-mono) use increased by line of therapy. The median TTNT across all regimens decreased by line of therapy (Table). BR and bendamustine + obinutuzumab (BO) had longer TTNT in 1L, while BR and R2 had longer TTNT in 3L. Inpatient admissions and outpatient visits increased with the line of therapy. Mean (SD) outpatient visits were 5.3 (3.2) in 1L, 5.8 (3.7) in 2L, 6.3 (4.0) in 3L, and 6.1 (3.3) in 4L, while inpatient admissions ranged from 0.1 (0.3) in 1L to 0.3 (0.4) in 4L. The mean total cost of care ranged from $40,538-$74,466, increasing by line of therapy. The mean total cost of care was consistently lowest in R-mono ($31,704-$36,197), while CAR-T had the highest total cost ($501,493-$522,378). R-mono had the lowest while R-CHOP had the highest mean outpatient visits across lines of therapy. Conclusions: Real-world TTNT decreased while costs and HCRU increased with each subsequent line of treatment, indicating a high disease burden in FL patients, particularly for those with R/R FL.These findings suggest the need for better treatment options for patients with FL, especially in 3L and 4L. [Table: see text]
The clinical significance of PRMT8 expression in esophageal squamous cell carcinoma and the influence on prognosis.
Authors: Sihan Liu, Jing Zuo, Xue Zhang
Journal: Journal of Clinical Oncology (2024)

e16066 Background: Protein arginine methyltransferase 8 (PRMT8), a member of protein arginine methyltransferases, is an enzyme catalyzing the methylation of arginine residuals of histones and non-histone proteins to serve as one of many critical post-translational modications (PTMs). Esophageal squamous cell carcinoma (ESCC) is the third most common cancer type of the gastrointestinal tract with poor prognosis. Abnormal arginine methylation modifications are closely associated with the development of ESCC and can exert oncogenic effects by regulating a variety of cellular processes. However, the expression of PRMT8 in ESCC and its influence on prognosis is currently unknown. Methods: After passing the application and obtaining the approval of the hospital ethics review committee and obtaining the informed consent of all patients and their families, we collected 46 cases of renal cell carcinoma diagnosed in the Fourth Hospital of Hebei Medical University from 2018 to 2023, and postoperative pathological reports of all patients confirmed to be ESCC. We followed the selected patients and obtained complete data. All the pathological specimens of the selected patients were resectioned and then subjected to immunohistochemical examination to observe the expression differences of PRMT8 in ESCC, and parallel semi-quantitative analysis. Finally, the data of the patients were statistically built. Results: PRMT8 is mainly stained on the plasma membrane of tumor cells. The difference in expression levels between ESCC and normal tissue adjacent to the cancer was statistically significant (P &lt; 0.01). This study found that the patient’s gender, age, tumor side have no correlation with the expression levels of PRMT8 (P &gt; 0.05), while the three indicators of tumor size, TNM stage, and lymph node metastasis are positively correlated with the expression levels of PRMT8 and the difference is statistically significant (P &lt; 0.01). Moreover, the positive staining of PRMT1 in ESCC was significantly correlated with poor prognosis of ESCC patients. Conclusions: The expression of PRMT8 is highly expressed in ESCC and associated with aberrant clinicopathological characteristics and poor prognosis. PRMT8 is a potential target for the stratification and treatment of ESCC.
Update results of anlotinib combined with penpulimab and nab-paclitaxel as first-line treatment for advanced esophageal squamous cell carcinoma (ESCC): A single-arm, open-label phase II clinical trial.
Authors: Zhiwei Chang, Xiao-Lei Liu, Dan-Dan Yu, Hui-Qiong Han, Jian He, Rui-Rui Wang, Yong-Xu Jia, Jie Yan, Yanru Qin
Journal: Journal of Clinical Oncology (2024)

e16017 Background: Recently, PD-1 blockades combined with dual chemotherapy in first-line setting exhibited encouraging efficacy for patients with ESCC. However, the safety profile of conventional dual chemotherapy remained unsatisfactory. Therefore, PD-1 blockades combined with anti-angiogenic tyrosine kinase inhibitors (TKIs) and single chemotherapy regimen might be a promising strategy. Anlotinib, a novel multitarget TKI primarily targeting VEGFR1-3, demonstrated promising therapeutic activity as first-line combination therapy or second-line monotherapy for patients with ESCC in China clinically. Therefore, this study was designed to explore the efficacy and safety of anlotinib combined with penpulimab (PD-1 blockade) and nab-paclitaxel as first-line therapy in advanced ESCC. Preliminary results were presented at the 2024 ASCO-GI Symposium (Abs 340), the consecutively updated results were presented in this report. Methods: Patients with previously untreated metastatic or locally advanced ESCC were recruited and treated with anlotinib (12mg, po, d1~14, q3w) and penpulimab (200mg, iv, d1, q3w) plus nab-paclitaxel (220mg/m 2 , iv, d1, q3w) until disease progression or unacceptable toxicity. The tumor response was assessed according to RECIST 1.1 using CT scans every two cycles. Adverse events were recorded by severity in accordance with the NCI CTC AE Version 5.0. The predefined sample size was 30. Primary endpoint was PFS and secondary endpoints included safety, ORR, DCR and OS. Results: From Jul 2022 to Dec 2023, a total of 27 patients were enrolled, 25 patients who had received first tumor response were included in this analysis. The best overall response indicated that there were 1 CR (4.0%), 18 PR (72.0%), 3 SD (12.0%) and 3 NE (12.0%). Therefore, the preliminary ORR was 76.0% (95%CI: 54.9%-90.6%), DCR was 88.0% (95%CI: 68.8%-97.5%). Median PFS of the 25 patients was not yet reached. Additionally, safety profile exhibited that the regimen was tolerable. The most common treatment-emergent adverse events among the 27 patients with the incidence &gt; 20% were anemia (40.7%), peripheral nerve toxicity (37.0) and white blood cell decreased (25.9%). Common grade ≥3 treatment-emergent adverse events were white blood cell decreased (7.4%), diarrhea (3.7%), glutamic-pyruvic transaminase was elevated (3.7%), glutamic oxalacetic transaminase increased (3.7%), hypertension (3.7%) and immune enteritis (3.7%). Conclusions: The combination of anlotinib plus penpulimab and nab-paclitaxel as first-line therapy for advanced ESCC demonstrated promising efficacy and manageable safety profile. And the conclusions needed to be confirmed in subsequent trials.