bluuebunny/crossref_metadata_2025_split huggingface dataset:
Benmelstobart (TQB2450) combined with anlotinib hydrochloride capsule in the treatment of advanced, recurrent, or metastatic endometrial cancer: A multicohort, open label, multicenter, phase II clinical trial (TQB2450-II-08).
Authors: Wu Xiaohua , Chen Xiaojun , Wang Ke , Wang Dong , An Ruifang , Hou Jianqing , Yang Ying , Wang Danbo , Qu Pengpeng , Zhang Bingzhong , Duan Wei , Li Xiumin , Zang Ai-min , Yu Guohua , Lou Hanmei , Yao Desheng , Wang Shuzhen , Yan Dong , Li Liang , Liu Xiaowei 
Published: June 2024

5593 Background: The treatment options after first-line chemotherapy for endometrial cancer (EC) are very limited. Several immune checkpoint inhibitors or combined with antiangiogenic drugs have shown antitumor activity and been approved in EC. Anlotinib is a multiple-targeted tyrosine kinase inhibitor that has been approved for the treatment of several solid tumors. Benmelstobart (TQB2450) is a humanized monoclonal antibody targeting programmed death-ligand 1 (PD-L1). This multicohort, open label, multicenter, phase II study aims to evaluate the efficacy and safety of TQB2450 injection or combined with anlotinib hydrochloride capsule in the treatment of recurrent or metastatic advanced EC. Methods: Patients with pathologically confirmed recurrent or metastatic advanced EC failed at 1 or 2 prior lines of therapy will be enrolled. Non-MSI-H/dMMR patients were treated with TQB2450+anlotinib therapy (TQB2450 1200mg, IV D1/Q3W; anlotinib 12mg PO QD, D1-14/Q3W) (cohort 1) or anlotinib (cohort 3), MSI-H/dMMR patients were treated with TQB2450 (cohort 2), until disease progression or intolerable toxicity experienced. Cohort 1 is divided into two stages for enrollment. In the first stage, 22 patients are enrolled. If the lower limit of the confidence interval is greater than 15%, indicating that there are at least 8 patients achieved CR/PR, consideration can be given to proceeding to the next stage. In the second stage, 85 patients are enrolled. The primary endpoint was the objective response rate (ORR) by independent review committee (IRC). Key secondary endpoints include ORR by investigator, disease control rate (DCR), duration of response (DoR), progression free survival (PFS), overall survival (OS) and safety. Results: As of November 09, 2023, 170 patients were enrolled and treated (cohort 1 N=107, cohort 2 N=32, cohort 3 N=31). In the first stage, 22 patients enrolled, 8 achieved CR/PR, and the study progressed to the second stage in cohort 1. Antitumor activities are shown in the table. Treatment-emergent adverse events (TEAEs) occurred in 99.07%, 100% and 100% of patients. Grade ≥3 TEAEs were reported in 74.77%, 40.63% and 87.10% of patients, respectively, with the most common ones being weight loss (46.73%, 25%, 29.03%), white blood cell decreased(47.66%, 12.5%, 19.35%), blood corticotrophin increased (44.86%, 15.63%, 22.58%), thyroid stimulating hormone increased (37.38%, 3.13%, 25.81%). Conclusions: TQB2450 plus anlotinib showed promising antitumor activity with a manageable safety profile in the treatment of recurrent or metastatic advanced EC. Clinical trial information: NCT04574284 . [Table: see text]
Combined uterine and colorectal screening: A call for action.
Authors: Jiang Ruolin Lorraine , Johnson Caitlin Ruth , Francoeur Alex Andrea , Mann-Grewal Amandeep Kaur , Kapp Daniel Stuart , Chan John K 
Published: June 2024

5615 Background: Colon cancer is currently one of the top three malignancies in the US with routine screening guidelines in place. With the current rise in uterine cancer incidence and mortality, there is currently no screening for uterine cancer. We propose to evaluate the demographics and trends in uterine and colorectal cancer incidences among women in the United States. Methods: Uterine and colorectal cancer incidence data among U.S. women were collected from the United States Cancer Statistics (USCS) database from 2001-2019. Annual estimated uterine and colon cancer incidence data among women was obtained from the American Cancer Society (ACS) from 2015-2024. SEER*Stat 8.3.9.2 and Joinpoint regression program 4.9.0.0 were used to calculate cancer incidences and trends per 100,000. Average annual percentage change (AAPC) was used to describe trends. Age-adjusted incidences were adjusted by the U.S. 2000 standard population. SAS Enterprise Guide v 7.1 was employed to analyze estimated cancer incidences. Results: From 2001-2019, 904,032 incident uterine cases were identified from USCS. Regarding race, 76.5% identified as non-Hispanic White, 10.5% as non-Hispanic Black, 8.38% as Hispanic, and 3.42% as non-Hispanic Asian/Pacific Islander. Of the 1,337,470 incident colorectal cancer cases obtained from USCS, 76.4% identified as White, 12.1% as Black, 7.10% as Hispanic, and 3.23% as Asian. Using ACS data from 2015-2024, the estimated number of annual incident uterine cancer cases increased from 54,870 to 67,880 while colorectal cancer incidence changed from 63,610 to 71,270 cases over the past 10 years (p<0.0001). Using a projection model, we predict that the incidence of uterine cancer will surpass colon cancer by 2025 at 40.17 and 37.07/100,000 respectively (Table). Given that Black women have a high rate of increasing uterine cancer incidence (AAPC 2.88%; p<0.0001), we predict that uterine cancer incidence among Black populations will surpass their rate of colon cancer by 2025 (42.97 vs 35.10/100,000). Conclusions: These findings suggest that uterine cancer incidence is increasing at a concerning rate and will likely surpass colon cancer by 2025. The impact of health disparities on Black women calls for research on the need for screening and novel therapies. [Table: see text]
Genomic alterations and clinical outcomes in patients with non-clear cell RCC: Indiana University experience.
Authors: Taza Fadi , Tran Mya , Hassoun Rebecca , Althouse Sandra K. , Fausel Christopher A. , Schneider Bryan P. , Salous Tareq , Logan Theodore F. , Adra Nabil , King Jennifer 
Published: June 2024

e16506 Background: Non-clear cell RCC (nccRCC) represents a heterogeneous group of tumors with sparse data on the clinical features and genomic landscape. Here, we describe a real-world cohort of nccRCC patients, characterize the genomic makeup, and report on clinical outcomes utilizing contemporary therapeutic strategies. Methods: Patients with nccRCC treated at Indiana University and who underwent genomic sequencing between 2015-2023 were included in this analysis. Baseline demographic and disease characteristics were summarized. Kaplan-Meier method was used to analyze progression-free survival (PFS) and overall survival (OS) using the log rank test to compare groups. Results: 55 patients were included. The median age at diagnosis was 56 years. 48 patients (87%) had metastatic disease. 25 (45.5%) had de novo metastatic disease. The most common histology subtypes included were unclassified (n=18; 32.7%), papillary (n=14; 25.5%), chromophobe (n=6; 10.9%), translocation (n=5; 9.1%), renal medullary (n=3; 5.5%), collecting duct (n=3; 5.5%), and other (n=6; 11.0%). Rhabdoid and/or sarcomatoid features were present in 32% (n=18). First-line systemic therapy for metastatic disease was single agent tyrosine kinase inhibitor (TKI) in 14 patients (29.2%), combination immunotherapy (IO-IO) for 11 patients (23.0%), combination IO-TKI for 11 patients (23.0%), single agent IO for 2 patients (4.2%), cisplatin-gemcitabine in 5 (10%), and other in 5 patients (10%). Genomic alterations are summarized in the table. Overall, diverse mutations were detected across variant subtypes, including alterations in TP53, CDKN2A, NF2, chromatin modulation ( SETD2, BAP1, PBRM1), PI3K/AKT (PIK3CA, PTEN, mTOR), and VHL/HIF pathway. Median PFS was 0.6 (0.3-0.9) years. No statistical difference was observed in the median PFS between the histology subgroups. 2-year OS for chromophobe histology was 100%, unclassified was 62.2%, papillary was 56%, and other histologies was 40.4%. 2-year OS for all patients treated with IO-TKI was 85.7%, single agent TKI was 47.9%, IO-IO was 38.6%, and NE for single agent IO. Conclusions: In this real-world cohort of patients with nccRCC, unclassified histology had the highest frequency of the most common genomic alterations evaluated. There was a trend with improved 2-year OS for patients with chromophobe histology and patients treated with IO-TKI. [Table: see text]
The impact of smoking status on genomic profile in patients with renal cell carcinoma.
Authors: Pham Phillip , Hassoun Rebecca , Althouse Sandra K. , Tran Mya , Fausel Christopher A. , Schneider Bryan P. , Logan Theodore F. , Salous Tareq , Adra Nabil , King Jennifer 
Published: June 2024

e16521 Background: Cigarette smoking is a known risk factor for the development of renal cell carcinoma (RCC), and active smoking has been associated with decreased survival in patients (pts) receiving systemic targeted therapies for RCC. The impact of smoking status on tumor genomics in other malignancies has been evaluated, particularly in urothelial carcinoma. Here, we investigated the impact of smoking status on genomic alterations and outcomes in pts with RCC. Methods: Pts with history of RCC who underwent genomic sequencing between 2015-2023 at Indiana University were included. Baseline demographic and disease characteristics were summarized. Pts were classified by smoking history into either no smoking history or history of smoking, which included both pts who currently or previously smoked. Comparisons between groups were done using the Chi-square test for categorical variables and Wilcoxon test for continuous variables. Kaplan-Meier method was used to analyze progression free survival (PFS) and overall survival (OS), using the log rank test to compare groups. Results: 144 pts were included. 63 (43.8%) were never smokers, 58 (40.3%) previously smoked, and 23 (16.0%) currently smoked. 103 (71.5%) were male. Median age at diagnosis was 58yrs (range: 24-83). Pts who currently smoked had a median age of 52 yrs vs. 59yrs for both pts who previously smoked and who never smoked (p=0.021). 133 pts (92.4%) were white. Histology was 69.4% clear cell, 9.0% unclassified, 9.1% papillary, 2.1% translocation, 2.1% collecting duct, 1.4% renal medullary, 1.4% chromophobe, 1.4% poorly differentiated, 0.7% mixed, and 3.4% other. Histology did not differ based on smoking status. Rhabdoid and/or sarcomatoid features were present in 28.8% of pts. 138 pts (95.8%) had metastatic disease. 65 pts (47.1%) presented with de novo metastatic disease. Metastasis sites included lung 56.9%, regional lymph nodes (LN) 40.3%, bone 31.9%, liver 17.4%, distant LN 18.8%, and brain 6.9%. The table lists genomic alterations in patients with and without a smoking history. Overall, 2-yr PFS was 9.2% and 2-yr OS was 86.5%. 2-yr PFS in pts with a smoking history was 9.2% vs. 8.6% in pts without a smoking history. 2-yr OS in pts with a smoking history was 90.1% vs. 82.3% in pts without a smoking history (p=0.49). Conclusions: In this cohort of pts, there was a trend toward more frequent PBRM1 mutations, which have been associated with improved response to immunotherapy, in pts with a history of smoking. Larger datasets are needed to further evaluate potential genomic differences based on smoking history that may reflect increased sensitivity to particular systemic therapies. [Table: see text]
HALP index in patients with metastatic clear-cell RCC treated with nivolumab.
Authors: Palacka Patrik , Obertova Jana , Chovanec Michal , Sycova-Mila Zuzana , Stefanikova Katarina , Slachtova Eva , Zak Monika , Savka Alexander , Hrncar Matej , Mego Michal , Rejlekova Katarina 
Published: June 2024

e16523 Background: To evaluate the prognostic value of the index combining hemoglobin and albumin levels with lymphocyte and platelet counts (HALP) in patients with metastatic clear-cell RCC treated with nivolumab. Methods: We enrolled 149 subjects (38 females), median age 62 years, treated with nivolumab 240 mg biweekly or 480 mg each 28 days following progression on at least one TKI from 2016 to 2024. The study population was dichotomized based on the median of HALP index (24.12), which was calculated as hemoglobin (g/L) x albumin (g/L) x absolute number of lymphocytes / platelets (g/L) at initiation of immunotherapy. Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method with differences analyzed by the log-rank test. Multivariate Cox proportional-hazards model was used to evaluate the prognostic value of the HALP, ECOG performance status and lactate dehydrogenase (LDH). Results: At the median follow up 17.4 months, 122 patients progressed on nivolumab and 87 died. ECOG 2 v ECOG 0 and 1 was associated with significantly worse PFS and OS ( P < 0.0001, HR 0.21 and P < 0.0001, HR 0.15, respectively). Both survivals were shorter in patients with serum LDH higher than 1.5-time of normal range compared to lower levels ( P = 0.0034, HR 0.47 for PFS and P < 0.007, HR 0.45 for OS). Low HALP correlated with worse PFS ( P = 0.0121, HR 0.62) and OS ( P = 0.0025, HR 0.50). The independent prognostic value of HALP index was showed in multivariate analysis. Conclusions: HALP index determined at initiation of nivolumab in second or third line was an independent prognostic factor for survival of metastatic clear-cell RCCs. A nomogram based on the HALP could accurately predict prognosis of these patients. Key Words: Blood Counts. Albumin. Metastatic Disease. Renal-Cell Carcinoma. Nivolumab.
Improved overall survival with immune checkpoint inhibitors in the treatment of metastatic urothelial carcinoma: A national retrospective comparative study.
Authors: Yu Chih-Chin , Su Po-Jung , Tsai Yao-Chou 
Published: June 2024

e16550 Background: Numerous randomized trials have illustrated the survival advantages of immune checkpoint inhibitors (ICI) in metastatic urothelial carcinoma. However, the application of ICI varies in different trials, encompassing first-line, second-line, monotherapy, combination with chemotherapy, or maintenance therapy. Real-world clinical practices often diverge from trial criteria. This study aims to evaluate the effectiveness of any ICI regimen in treating metastatic urothelial carcinoma using real-world data. Methods: This retrospective comparative study included patients diagnosed with locally advanced or metastatic urothelial carcinoma between January 2015 and July 2023, sourced from the Taiwan Upper Tract Urothelial Cancer and Bladder Cancer Collaboration Database. Patients with prior neo-adjuvant or adjuvant systemic therapy were excluded. Results: Among 427 patients, 152 (35.6%) who received any ICI as the first-line or second-line regimen constituted the ICI group, while the remaining 275 (64.4%) patients receiving only chemotherapy formed the chemotherapy group. Within the ICI group, 55 (36.2%) patients received monotherapy, 49 (32.2%) received combination therapy with chemotherapy, and 4 (2.6%) received maintenance therapy as the first-line regimen. The remaining 44 (28.9%) patients received ICI as the second-line regimen. No significant differences were observed in age, sex, performance status, renal function, tumor site, ratio of locally advanced disease, ratio of visceral metastasis, and ratio of previous radical surgery between the two groups. Median overall survival (OS) from the start of the first-line therapy was 15.8 months in the ICI group and 10.2 months in the chemotherapy group. Kaplan-Meier curves demonstrated that the ICI group exhibited superior OS and cancer-specific survival compared to the chemotherapy group (log-rank p= 0.009 and 0.004, respectively). In the multivariable analysis, the ICI group also demonstrated favorable outcomes in OS [hazard ratio (HR) 0.726, p=0.011] and cancer-specific survival (HR 0.67, p=0.004). Conclusions: Our study confirms the clinical efficacy of ICI in metastatic urothelial carcinoma. The use of ICI monotherapy or combination in the first-line or second-line regimen for metastatic urothelial carcinoma improves patient survival. [Table: see text]
Immunotherapy plus chemotherapy versus chemotherapy alone as first-line treatment for advanced urothelial cancer: A systematic review and meta-analysis of randomized controlled trials.
Authors: Alves Ana Caroline Fonseca , Silva Isadora Mamede Mendes da , Escalante Romero Lorena , Celso Davi Said Gonçalves , Reis Pedro Cotta Abrahão , Dacoregio Maria Inez , Stecca Carlos 
Published: June 2024

e16554 Background: Platinum-based chemotherapy (CTX) has stood as the cornerstone in the treatment of advanced urothelial cancer (aUC) for decades, with limited alternative options available. The landscape shifted with the integration of PD-1 and PD-L1 inhibitors into the therapeutic arsenal, emerging as pivotal post-platinum therapies. The exploration of their potential role in the initial treatment of aUC is now a subject of active investigation. In response to these advancements, we conducted a meta-analysis to evaluate the effectiveness of immunotherapy in the first-line management of aUC patients. Methods: A systematic search across PubMed, Embase, and Cochrane identified randomized controlled trials (RCTs) comparing PD-1 and PD-L1 inhibitors combined with CTX versus CTX alone for aUC. Outcomes included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and treatment-related adverse events (TRAE). Heterogeneity was assessed using I2 statistics, employing a random-effects model for analysis. Statistical analyses were performed using R software version 4.3.2. Results: Among 2,162 patients from three RCTs, 1,106 (51.16%) received immunotherapy. Combining immunotherapy to CTX demonstrated substantial improvements in both PFS (HR 0.78; 95% CI 0.70-0.86; p < 0.01) and OS (HR 0.84; 95% CI 0.75-0.93; p < 0.01) compared to CTX alone in the entire cohort. Enhanced PFS was observed in both Cisplatin (HR 0.71; 95% CI 0.62-0.82; p < 0.01) and Carboplatin (HR 0.85; 95% CI 0.73-0.98; p = 0.03) subgroups. Significant OS benefit was restricted to the cisplatin subgroup (HR 0.80; 95% CI 0.69-0.93; p < 0.01), while in the Carboplatin subgroup, the benefit was only numerical (HR 0.87; 95% CI 0.75-1.01; p = 0.06), with no significant differences between subgroups (pinteraction = 0.44). Additionally, immunotherapy exhibited a higher ORR (RR 1.20; 95% CI 1.06-1.36; p < 0.01), with no significant differences in grade ≥ 3 TRAE (RR 1.06; 95% CI 0.98-1.15; p = 0.13). Conclusions: These findings underscore the effectiveness of combining PD-1 and PD-L1 inhibitors with CTX, revealing improved progression-free and overall survival in aUC compared to CTX alone. As anticipated, outcomes were better in patients treated with cisplatin, reaffirming its possible superiority over carboplatin regimens. Our results provide compelling evidence supporting the combination of immunotherapy and CTX as a first-line treatment option for patients with aUC.
Single-center retrospective analysis of safety and efficacy of dose-reduced enfortumab vedotin (EV) in frail patients with metastatic urothelial carcinoma (mUC).
Authors: Song Wilbur , Tao Yu , Luo Jingqin , Roth Bruce J. , Reimers Melissa Andrea 
Published: June 2024

e16556 Background: EV is a Nectin-4 directed ADC with activity in mUC. EV monotherapy increased PFS and OS compared to salvage chemotherapy in pretreated mUC. EV + pembrolizumab increased PFS and OS compared to chemotherapy as first-line therapy and is being explored in the perioperative setting. Thus, EV will likely have an increasingly prominent role in the management of UC. However, EV is given until disease progression and has significant toxicities, especially for elderly or frail patients. Other than the initial dose escalation, no studies have reported the efficacy or safety of starting EV at a dose lower than the approved dose of 1.25 mg/kg. Methods: We performed a single-center retrospective analysis of patients treated with EV from 1/1/2020 to 12/25/2023. Data were collected by chart review including labs, imaging, and clinical documentation. Grades of toxicity were assigned based on CTCAE v5.0 criteria with available data. Radiographic response was determined by the investigator. We evaluated outcomes including ORR, PFS, OS, and EV-associated AEs, and compared these between patients who received 0.75 mg/kg (“low-dose”) and patients who received higher doses (“standard-dose”). Given the small sample size, we present only descriptive statistics. Results: We analyzed data from 18 patients treated with standard-dose EV and from 9 patients treated with low-dose EV. The low-dose group, compared with the standard-dose group, had a similar number of females (33% vs 44%) and non-whites (33% vs 28%), and higher median age at first EV dose (81 vs 68). The low-dose group had a lower rate of prior curative intent surgery (55% vs 78%) and upper tract disease (11% vs 50%), and fewer prior lines of treatment in the palliative setting (median 1 vs 2). In the low-dose group, ORR was 78% with CR in 33%. With a median follow up of 15.9 months, median PFS and median OS from EV initiation were not estimable. In the standard-dose group, ORR was 78% with CR in 28%. With a median follow up of 28.2 months, median PFS was 8.9 months and median OS was 24.1 months. The low-dose group had similar or lower grades of EV-associated AEs (Table). Conclusions: Patients treated with low-dose EV 0.75 mg/kg had similar responses compared to historical controls and a same-institution cohort of patients treated with standard-dose EV, with lower rates of GI toxicities, rash, and peripheral neuropathy. Findings are limited by small sample size, retrospective nature, and differences in baseline characteristics. Low-dose EV in elderly or frail patients with baseline comorbidities warrants prospective study. [Table: see text]