bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trends in the thrombotic complications of myeloproliferative neoplasms: A nationwide analysis.
Authors: Solipuram Divya , Mehta Kathan , Siddappa Malleshappa Sudeep Kumar 
Published: June 2024

6581 Background: Thrombotic complications are a well known cause of morbidity and mortality in Philadelphia-negative Myeloproliferative Neoplasms[Polycythemia Vera, Essential thrombocythemia, Primary Myelofibrosis]. Current study evaluated thrombotic events incidence and outcome trends in Myeloproliferative Neoplasms[MPN] from 2012 to 2020. Methods: This is a longitudinal study of thrombotic events in MPN using the Nationwide Inpatient Sample. All patients with a diagnosis of MPN admitted with any thrombotic event including arterial or venous thrombosis were included in the study. Arterial thrombotic events included Myocardial infarction[MI], Ischemic stroke[IS], Transient Ischemic Attack[TIA] while venous thrombotic events included Deep Vein Thrombosis[DVT], Pulmonary Embolism[PE], Budd-Chiari Syndrome[BCS], Portal Vein Thrombosis[PVT]. Thrombosis related inpatient mortality rate, incidence, length of hospital stay, and total hospital charges were calculated. Results: Mortality rate from any thrombotic event overall[arterial plus venous] increased from 2.3% to 2.6% from 2012 to 2020. There was an increase in mortality rates from 2.8% to 3.8% among arterial thrombosis while there was a decrease in venous thrombosis related mortality from 1.7 to 0.4%. Specifically MI and IS related mortality increased from 3.7% to 4.3% and 3% to 4% respectively over the same period. The incidence of any thrombotic event declined from 2 to 1.3 cases/100,000 persons from 2012 to 2020. A similar decline in incidence of arterial, venous events, MI, IS were observed. The mean length of stay decreased from 5.8 days in 2012 to 5.2 days in 2020 among MPN patients with venous thrombosis which was statistically significant. Similar decline was noted in MI patients as well. Though the mean length of stay increased from 7.9 to 9.5 days among MPN patients with IS, this increase was not statistically significant. The mean hospitalization charges for thrombotic events increased from $53,421 in 2012 to $101,598 in 2020 after adjusting for inflation. Similar trends were noted in all types of thrombotic admissions which were all statistically significant. Upon age based stratification of MPN, mortality for those less than 60 years reduced from 2% to 0.3%, while it increased from 4.1 to 5.6% in those more than 60 years from 2012 to 2020. Conclusions: Inpatient mortality from thrombotic events in MPN has shown an increasing trend from 2012 to 2020 though there was a decline in overall incidence of thrombosis during the same period. Despite the decreasing trend in length of stay, the total economic burden of thrombotic complications in MPN is increasing in the US. Specifically the effects were more pronounced in those greater than 60 years. This points to the need for revisiting guidelines regarding thromboprophylaxis in MPN.
A multi-center cohort study Examining risk factors for central nervous system metastases (CNSm) in patients with stage III non-small cell lung cancer (NSCLC) treated with definitive chemoradiation (ChemoRT) followed by durvalumab (Durva).
Authors: Sharp John , Young Philip , Zhao Songzhu , Patel Sandip Pravin , Wei Lai , Li Mingjia , Brownstein Jeremy , Haglund Karl , Palmer Joshua David , Raval Raju R. , Shields Peter G. , He Kai , Kaufman Jacob , Memmott Regan Michelle , Alahmadi Asrar , Carbone David Paul , Otterson Gregory Alan , Presley Carolyn J. , Gentzler Ryan D. , Owen Dwight Hall 
Published: June 2024

8076 Background: In the PACIFIC trial, 6.3% of patients with unresectable stage III NSCLC receiving durva after chemoRT developed CNSm. In a single center study, we previously reported real-world incidence of CNSm is higher at 19.8%. Risk factors for development of CNSm post-durva are incompletely understood. Methods: We conducted a multi-center retrospective study of patients with unresectable stage III NSCLC treated with durva after chemoRT from 2018 to 2022 with no CNSm on baseline brain MRI to assess for incidence of CNSm. Patient characteristics were compared between cohorts with and without CNSm to assess for risk factors for CNSm using Fisher’s exact test for categorical variables and two-sample t-test or Wilcoxon Mann-Whitney U-test for continuous variables. Overall survival was compared using log-rank test. Results: Of 193 patients in our study, 32 (16.6%) developed CNSm with median time to CNSm of 6.4 mo (IQR 4.5 - 13.7). Twenty-five (78%) had CNSm within one year. Patients with CNSm had a longer interval between baseline brain MRI and start of durva (median 3.7 mo vs 3.3 mo, p=0.02) and received fewer doses of durva compared to those without CNSm (median 7 vs 12, p=0.03). As some patients received Q2 week and others Q4 week durva, we also compared median durva treatment duration, which was consistent (3.7 mo vs 8.3 mo, p=0.02). There was no association between CNSm and age, sex, histology, T/N stage, PDL1 status, or chemoRT regimen (Table). Patients with CNSm had shorter median survival (19.6 mo vs 36.4 mo, p=0.008). Conclusions: Real-world incidence of CNSm is higher than that seen in PACIFIC. Patients with CNSm received less durva, likely due to early disease progression, and had longer intervals between baseline brain MRI and starting durva. Minimizing treatment delays may improve outcomes. Further research is needed to understand optimal surveillance strategies for CNSm in this patient population. [Table: see text]
Programmed cell death ligand 1 (PD-L1) inhibitors versus programmed cell death 1 (PD-1) inhibitors for the first-line therapy of extensive-stage small cell lung cancer: A propensity score-matched study.
Authors: Tian Yaru , Lu Shuangqing , Sun Yulan , Tang Xiaoyong , Sun Zhuoran , Zhao Ke , Du Guochang , Li Wanjing , Zhu Hui 
Published: June 2024

8086 Background: Addition of programmed cell death ligand 1 (PD-L1) inhibitors or programmed cell death 1 (PD-1) inhibitors to etoposide‐platinum (EP) chemotherapy has become the standard first-line regimen for ES-SCLC. The clinical efficacy and safety between the two types of immune checkpoint inhibitors (ICIs) remain controversial. We conduct the retrospective study and propensity score-matched analysis to explore the potential differences between them. Methods: Patients diagnosed with ES-SCLC and treated by EP plus PD-L1 or PD-1 inhibitors at Shandong Cancer Hospital between March 2019 and November 2022 were reviewed retrospectively. According to PD-L1 or PD-1 inhibitors, they were divided into two groups. Propensity score matching (1:1) was performed to balance the baseline characteristics of the two groups. The baseline characteristics and adverse events between the two groups were compared using the chi-squared test. The survival curves of overall survival (OS) and progression-free survival (PFS) were plotted by the Kaplan-Meier method and differences were analyzed by the log-rank test.The primary endpoints were OS and PFS. Results: As a result, 448 patients were analyzed in this study. 264 patients received PD-L1 inhibitors plus EP and 184 received PD-1 inhibitors plus EP. The median follow-up was 17.6 months. The median OS and PFS was 20.4 months and 7.8 months in the overall population. Before propensity score matching, the median OS was 20.1 months in PD-L1 inhibitor plus EP group and 20.7 months in PD-1 inhibitor plus EP group, respectively (HR 1.043, 95%CI 0.776-1.401; p= 0.781). The median PFS was 7.6 months in the PD-L1 inhibitor plus EP group and 8.5 months in PD-1 inhibitor plus EP group (HR 1.099, 95%CI 0.886-1.364; p= 0.390). After propensity score matching, the median OS and PFS were 20.4 months and 7.8months in PD-L1 inhibitor plus EP group, and those were 20.1 months and 8.6 months in PD-1 inhibitor plus EP group. There was no significant difference in OS and PFS between PD-L1 inhibitors plus EP and PD-1 inhibitors plus EP in the matched population (HR 1.104; p= 0.578 and HR 1.072; p= 0.602, respectively). The overall adverse events were comparable in the two groups. Only ≥3 grade neutropenia was more frequent in the PD-L1 inhibitors plus EP group (77.7% vs 69.0%, p= 0.040). Conclusions: In conclusion, the overall efficacy and safety profile was similar between PD-L1 inhibitors and PD-1 inhibitors for the first-line treatment of ES-SCLC.
ARTEMIS-001: Data from a phase 1a/b study of HS-20093 in patients with relapsed small cell lung cancer (SCLC).
Authors: Wang Jie , Duan Jianchun , Sun Yuping , Xing Ligang , Han Liang , Wang Qiming , Wu Lin , Chen Jianhua , Lu Ping , Guo Wei , Wang Haiying , Liu Baogang , Zhang Zhiye , Zhang Junhong , Huang Jianying , Shi Huaqiu , Yang Haiyu , Zhang Guoping , Ning Fangling , Zhu Weiliang 
Published: June 2024

8093 Background: SCLC is characterized by a high rate of proliferation and poor prognosis, and new therapies are urgently needed. B7-H3 is highly expressed in SCLC. HS-20093, a B7-H3-targeted antibody-drug conjugate (ADC), demonstrated antitumor activity in advanced solid tumors in the dose escalation part of ARTEMIS-001 study (Jie Wang et al., JCO, 2023) (NCT05276609). Here, we present results on the efficacy and safety of the expansion doses in patients (pts) with SCLC from phase 1a/b. Methods: ARTEMIS-001 study consisted of dose escalation (1a) and expansion (1b) part. Pts were treated with doses of 1.0 to 16.0 mg/kg HS-20093 every 3 weeks in dose escalation, and were treated with doses at 8.0 mg/kg and 10.0 mg/kg randomly in dose expansion. Pts with SCLC were required to have received prior platinum-based standard therapy. B7-H3 expression was retrospectively evaluated by IHC. Results: As of data cutoff November 30th 2023, a total of 56 pts with extensive stage SCLC (ES-SCLC) were enrolled and received ≥1 dose of HS-20093 with doses at 8.0 mg/kg (n=31) or 10.0 mg/kg (n=25). Median prior lines of therapy was 2.0 (range: 1-6). All pts received platinum plus etoposide and 73.2% (41/56) received immunotherapy. Safety profile was consistent with previous reports. The most common grade≥3 treatment-related adverse events (≧10%) were neutropenia, leukopenia, lymphopenia, thrombocytopenia and anemia. Out of 56 pts, 52 pts were efficacy evaluable (8.0 mg/kg: 31 pts; 10.0 mg/kg: 21 pts). HS-20093 showed encouraging efficacy in relapsed ES-SCLC (Table). Tumor shrinkage in target lesions occurred in 96.2% (50/52) pts with a post-baseline scan. Deep response defined as tumor shrinkage ≥50% was obtained in 44.2% (23/52) pts. Median overall survival has not yet reached. Responses were observed regardless of B7-H3 expression. Pharmacokinetic (PK) showed approximately dose-proportional increase in exposure with a half-life of 3-7 days. PK profiles of total antibody and ADC were similar and exposure to payload was considerably low. Conclusions: HS-20093 demonstrated promising antitumor activity and manageable safety in pts with previously-treated SCLC. Phase 3 study is planned to compare the efficacy and safety of HS-20093 with standard-of-care chemotherapy in relapsed SCLC. Clinical trial information: NCT05276609 . [Table: see text]
Survival outcomes of patients with extensive-stage small cell lung cancer who received treatment with atezolizumab in combination with carboplatin and etoposide: A propensity score adjusted cohort study.
Authors: Batah Heya , Adcock Bridget , Lee Monica , Patel Preeyal , Patel Meera , Zureigat Hadil , Hassan Ahmed , Nurse Daniel Paul , Rauf Asad , Tomer Jacqulyn , Hoen Douglas Robert , Hassan Khaled Aref , Pennell Nathan A. , Shapiro Marc A. , Stevenson James , Zabor Emily Craig , Adjei Alex A , Mustafa Ali Moaath Khader 
Published: June 2024

8096 Background: Small cell lung cancer (SCLC) is an aggressive type of lung cancer. Most patients (pts) are diagnosed with extensive-stage disease (ES-SCLC). The cornerstone treatment of ES-SCLC has been platinum-based chemotherapy and etoposide. Combining atezolizumab with carboplatin plus etoposide (Carbo-E) improved overall survival (OS) in ES-SCLC pts and became a new standard for first-line treatment. However, there is a paucity of real-world outcomes in ES-SCLC. Herein, we present the largest and longest follow-up retrospective study analyzing atezolizumab in combination with chemotherapy for treatment of ES-SCLC. Methods: We conducted a retrospective study and included all adult pts (≥ 18 years) with ES-SCLC treated at Cleveland Clinic between 1/2010-12/2022. ES-SCLC was defined as stage IIIB or stage IV. We collected treatment regimens and baseline characteristics including age, sex, race, smoking, alcohol intake history, and comorbidities. Responses were assessed using RECIST response criteria. Both OS and progression-free survival (PFS) were calculated from treatment initiation. We used propensity score (PS) weighting and multivariable Cox proportional hazards ratio (CPH) to adjust for baseline confounding. Results: We identified 561 ES-SCLC pts who received treatment, 375 (67%) received Carbo-E and 160 (29%) received Carbo-E + Atezolizumab (Carbo-E-Atezo). The table describes the baseline characteristics of Carbo-E and Carbo-E-Atezo groups. The median follow-up was 30 months (mo) (IQR: 14 - 59). In the Carbo-E arm, 45 patients (12%) received second-line immune therapy (nivolumab +/- ipilimumab or pembrolizumab). On PS-adjusted logistic regression, pts who received Carbo-E-Atezo had a 1.1 odds ratio (95%CI: 0.85-1.43, P>0.05) to respond compared to pts who received Carbo-E. There was no difference in PS-adjusted median OS between pts who received Carbo-E-Atezo (9.2 mo (95%CI: 8.1-11)) vs. Carbo-E (8.4 mo (95%CI: 7.7-9.0)) (log-rank P>0.05). Similarly, there was no difference in adjusted median PFS between pts who received Carbo-E-Atezo (5.9 mo (95%CI: 5.3-6.9)) vs. Carbo-E (5.5 mo (95%CI: 4.7-5.9)) (P>0.05). Using CPH model, the addition of atezolizumab to Carbo-E did not decrease mortality (Hazard Ratio: 0.84, 95%CI: 0.68-1.04, P>0.05). Male gender and increasing age were predictors of worse OS (P<0.05). Conclusions: Among pts with ES-SCLC, the addition of atezolizumab to the standard chemotherapy regimen of Carbo-E showed no significant difference in PFS or OS in our real-world study. [Table: see text]
Efficacy and safety of taletrectinib in patients with advanced or metastatic ROS1+ non–small cell lung cancer: The phase 2 TRUST-I study.
Authors: Li Wei , Xiong Anwen , Yang Nong , Fan Huijie , Yu Qitao , Zhao Yanqiu , Wang Yongsheng , Meng Xue , Wu Jingxun , Wang Ziping , Liu Yunpeng , Wang Xicheng , Qin Xintian , Lu Kaihua , Zhuang Wu , Ren Yizhong , Zhang Xianyu , Yan Bing , Lovly Christine M. , Zhou Caicun 
Published: June 2024

8520 Background: Taletrectinib, a highly potent, next-generation, central nervous system–active, selective ROS1 tyrosine kinase inhibitor (TKI), was previously reported to provide high overall and intracranial (IC) response rates, prolonged progression-free survival (PFS), and activity against G2032R with favorable tolerability. We report updated data from the TRUST-I study (NCT04395677), the largest clinical trial to date conducted in patients living with ROS1+ NSCLC. Methods: TRUST-I, a multicenter, single-arm, open-label, pivotal phase 2 study of taletrectinib conducted in China, had 2 cohorts: TKI-naïve and TKI-pretreated. The primary endpoint was objective response rate (ORR) by Independent Review Committee (IRC) per RECIST 1.1. Secondary endpoints included duration of response (DoR), PFS, overall survival (OS), and safety. Results: As of November 2023, 173 patients were enrolled (median age: 55 y; 58% female; 73% never smoked; TKI-naïve: n = 106; TKI-pretreated: n = 67). In TKI-naïve patients, 21% had prior chemotherapy, and 17% had brain metastases; in TKI-pretreated patients, 34% had prior chemotherapy, and 42% had brain metastases. In TKI-naïve patients, the ORR was 91% (95% CI: 83, 95) and IC-ORR was 88% (7/8; 95% CI: 47, 100). In TKI-pretreated patients, the ORR was 52% (95% CI: 40, 65) and IC-ORR was 75% (12/16; 95% CI: 48, 93). In patients with G2032R mutation, 8 of 12 patients (67% [95% CI: 35, 90]) responded. DoR and PFS remain durable, with median follow-up of 23.5 months in TKI-naïve patients and 9.7 months in TKI-pretreated patients (Table). Among all patients (n = 173), the most frequent treatment-emergent adverse events (TEAEs) were AST increase (76%), diarrhea (70%), and ALT increase (68%). Rates of neurologic TEAEs were low (dizziness: 23%; dysgeusia: 10%) and mostly grade 1. Discontinuation (5%) and dose reductions (19%) due to TEAEs were low. Conclusions: With longer follow-up, taletrectinib continues to show high and durable overall responses, robust intracranial and G2032R activity, and a favorable safety profile with a low incidence of neurologic AEs. An additional ongoing pivotal phase 2 study, TRUST-II (NCT04919811), is further evaluating the efficacy and safety of taletrectinib in patients in the US, Europe, and Asia. Clinical trial information: NCT04395677 . [Table: see text]
Efficacy and safety of sigvotatug vedotin, an investigational ADC, in NSCLC: Updated phase 1 results (SGNB6A-001).
Authors: Peters Solange , Hollebecque Antoine , Sehgal Kartik , Lopez Juanita Suzanne , Calvo Emiliano , Dowlati Afshin , Bockorny Bruno , Perez Cesar Augusto , Sanborn Rachel E. , Patnaik Amita , Fontana Elisa , Galvao Vladimir , Kingsley Ed , Patilea-Vrana Gabriela , Wang Tianhua , Knowles Scott , Piha-Paul Sarina A. 
Published: June 2024

8521 Background: Integrin beta-6 (IB6), a tumor-associated membrane protein, plays an important role in pathogenesis and invasiveness and its expression correlates with poor outcomes. Sigvotatug vedotin (SV), formerly called SGN-B6A, is an IB6-directed ADC with encouraging activity in NSCLC in the Ph 1 study SGNB6A-001 (NCT04389632) (Hollebecque 2023). Here, we report updated efficacy and safety of SV in NSCLC. Methods: SGNB6A-001 is an open-label, multicenter, Ph 1 study evaluating the safety, pharmacokinetics (PK), and antitumor activity (cORR, DOR, and PFS per RECIST v1.1, and OS) of SV in patients (pts) with advanced solid tumors. Multiple dose regimens were explored during dose escalation (Part A). Dose expansion (Part B) is ongoing with selected regimens in various tumors including NSCLC. Parts C and D will evaluate SV in combination with pembrolizumab in NSCLC and HNSCC. Eligible pts had no therapeutic options (Part A) or had received platinum-based and anti-PD-(L)1 therapy unless contraindicated (Part B) and were dosed with the SV expansion regimens on D1 and D8 in a 21-day cycle (2Q3W; 1.2/1.25 mg/kg total body weight [TBW]) or D1 and D15 in a 28-day cycle (2Q4W; 1.5 mg/kg TBW, 1.8 mg/kg adjusted ideal body weight [AiBW]). Results: As of 01-Dec-2023, 306 pts had received SV; 113 pts with NSCLC received expansion regimens in Parts A and B. Prior lines of therapy and efficacy data for all pts with NSCLC and select subgroups are summarized in the table; cORR was 19.5% (95% CI, 12.6-28.0) in all pts with NSCLC and 32.5% (95% CI, 18.6-49.1) in pts with non-squamous (non-Sq)/taxane-naive NSCLC. Additional time-to-event data will be presented. Rates of TEAEs, ≥G3 TEAEs, SAEs, and TEAEs leading to discontinuation were 98.2%, 46.0%, 33.6%, and 13.3% in pts with NSCLC, and were consistent in all treated pts. The most common ≥G3 TEAEs in pts with NSCLC were dyspnea (9.7%), fatigue (7.1%), and neutropenia (5.3%). One pt with NSCLC had a treatment-related death (pneumonitis). PK variability across weight groups was lowest with 1.8 mg/kg AiBW 2Q4W. Conclusions: SV continues to demonstrate encouraging antitumor activity and a manageable safety profile in pts with NSCLC. Data at 1.8 mg/kg AiBW 2Q4W support initiation of the Ph 3 SGNB6A-002 study in 2/3L NSCLC (NCT06012435) and combination with pembrolizumab in earlier settings. Clinical trial information: NCT04389632 . [Table: see text]
Gene expression correlates of adagrasib response in KRASG12C mutated non-small cell lung cancer (NSCLC).
Authors: Kim Eejung , Tong Xinyuan , Patel Ayushi , Liu Shengwu , Dilly Julien , Hover Laura , Mukhopadhyay Suman , Sherman Fiona , Christensen James G , Olson Peter , Aguirre Andrew , Wong Kwok , Ji Hongbin 
Published: June 2024

8529 Background: KRASG12C inhibitors such as adagrasib and sotorasib have shown clinical promise in targeting KRASG12C-mutated lung cancers; however, most patients develop primary or secondary resistance. A biomarker of response to KRASG12C inhibitor is needed for better patient stratification and to understand the resistance mechanism. Methods: We analyzed transcriptional correlates of adagrasib treatment outcome in 68 patients in the KRYSTAL-1 trial, a phase 1/2 clinical trial of adagrasib monotherapy in the second line and beyond treatment for NSCLC. We also treated KRAS-mutated lung cancer mouse models and organoids with a KRAS inhibitor for the long term and characterized the resistant tumors’ transcriptional profile to identify resistance mechanisms. We also performed serial gene expression analysis of KrasG12D mutated lung organoids undergoing squamous transformation to identify transcription factor involved in the resistance process. Results: In patients with lung adenocarcinoma with KRASG12C and STK11/ LKB1 co-mutations, we find an enrichment of the squamous cell carcinoma gene signature in pre-treatment biopsies correlates with a poor response to adagrasib. Studies of Lkb1-deficient KRASG12C and KrasG12D lung cancer mouse models and organoids, treated with KRAS inhibitors adagrasib and MRTX1133, respectively, reveal that tumors invoke a lineage plasticity program, adeno-to-squamous transition (AST), that enables resistance to KRAS inhibition. We identify TP63 to be a transcription factor whose expression correlated with squamous transformation. The analysis of lineage plasticity program, adagrasib resistant tumors, and p63 regulon revealed KRT6A to be a common biomarker whose expression correlated with overall survival in the KRYSTAL-1 cohort. Conclusions: KRASG12C mutated lung adenocarcinoma patients with a higher expression of squamous cell carcinoma gene expression signature respond poorly to adagrasib treatment. Expression of the AST plasticity signature and KRT6A at baseline correlates with poor adagrasib responses. These data indicate the role of AST in KRAS inhibitor resistance and provide predictive biomarkers for KRAS-targeted therapies in lung cancer.