bluuebunny/crossref_metadata_2025_split huggingface dataset:
IFCT-2105 lurbiclin real-world effectiveness and treatment sequences in patients (pts) with extensive-stage small cell lung cancer (ES-SCLC) who received lurbinectedin as part of the French Early Access Program (EAP-ATU).
Authors: Girard Nicolas , Guisier Florian , Swalduz Aurélie , Van Hulst Sylvie , Pichon Eric , Lavaud Pernelle , Greillier Laurent , Tiotiu Angelica , Madroszyk Anne , Bylicki Olivier , Canellas Anthony , Belmont Laure , Zysman Maeva , Hauss Pierre-Alexandre , Godbert Benoit , Audigier-Valette Clarisse , Lebreton Cléa , Morin Franck , Westeel Virginie 
Published: June 2023

8584 Background: Novel options are needed for pts with ES-SCLC after the failure of first-line chemotherapy. Lurbinectedin demonstrated efficacy in a landmark phase II study [Trigo et al. Lancet Oncol. 2020 May;21(5):645], and was granted EAP-ATU in France in June 2020. Methods: Multicenter, retrospective cohort of consecutive pts with histologically or cytologically confirmed ES-SCLC, who received at least one dose of treatment with lurbinectedin as part of the French EAP-ATU from June 2020 until March 2021, and gave consent for the data collection, were enrolled in 47 sites. Primary and secondary endpoints were description of clinical characteristics, and exposure to treatment, response, PFS, OS, safety. Results: 312 pts – 64% male, median age 65 years, 72% PS0-1, 47% with brain metastasis, 58% with previous immunotherapy – were enrolled. Lurbinectedin was administered as second-line in 44% of pts; 58% were chemotherapy-refractory. Pts received a median number of 3 cycles of lurbinectedin. Concurrent radiotherapy on metastases was delivered to 38% of pts. Lurbinectedin was discontinued because of progression/death/toxicity/other reasons in 83%/8%/5%/4% of pts. Grade3/4 events were observed in 9%/5% of pts. Response rate was 22% [95%CI 17-27%], disease control rate was 38% [95%CI 32-44%]. After a median follow-up of 20.8 months, median PFS and OS were 1.9 [95%CI 1.8-2] and 4.7 [95%CI 4-5.4] months; 6-month PFS and OS were 7% [4-10%] and 42% [95%CI 37-48%]. PS≤2 and chemotherapy-free interval≥90days were associated with significantly longer OS (HR = 0.71 [95%CI 0.53-0.95] and HR = 0.58 [95% CI 0.44-076] respectively). Main sites of progression were the lung (39% of pts), the brain (39% of pts), the liver (30% of pts), and the mediastinum (30% of pts). Subsequent treatment was administered to 154 pts after discontinuation of lurbinectedin, mostly consisting of topotecan (26% of pts); response/disease control rates, and median PFS of first subsequent treatment were 11% [95%CI 6-17%], 35% [95%CI 27-44%], and 1.9 [95%CI 1.7-2.3] months. Conclusions: Lurbinectedin provides an additional option from second-line for ES-SCLC, with efficacy outcomes comparable to that of historical treatments.
Assessing inpatient outcomes for patients with small cell lung cancer presenting with superior vena cava thrombosis.
Authors: Vakil Jay , Turk Ekrem , Olafimihan Ayobami Gbenga , Deenadayalan Vaishali , Litvin Rafaella , Obeidat Khaldun , Ibrahim Muhammad Bilal , Batra Kunnal 
Published: June 2023

8589 Background: Superior Vena Cava Syndrome (SVCS) is a condition characterized by obstruction of the SVC that can commonly be caused by thrombus formation in the SVC. Small cell lung cancer (SCLC) frequently results in obstruction of the SVC. When severe enough, SVCS can present as a life-threatening oncological emergency. In this study we aim to explore baseline characteristics of SVC thrombosis (SVCT) in patients with SCLC, the prevalence of US hospitalizations, and disparities with regards to race and socioeconomic status. Methods: National Inpatient Sample was utilized to obtain pertinent data. Total hospitalizations with coexistent comorbidities of SCLC were extracted from the 2016 to 2019 database. Adult patients with a secondary diagnosis of SVC thrombosis were determined by using ICD-10 codes. We studied the racial and socioeconomic differences as well as length of stay (LOS), total hospital charges (THC), and all-cause mortality outcomes in cancer patients with and without SVC thrombosis. Statistical analysis was performed on STATA, with logistic regression analyses and chi-square tests. Results: A total of 480,750 patients were hospitalized for SCLC. 720 of these patients had SVC thrombosis (0.15% of SCLC patients). The mean age of those with thrombi was significantly lower compared to those without thrombi (64 vs. 69, p < 0.001). The SCLC with SVCT cohort had statistically higher proportion of black patients than the other cohort. Charlson index was significantly higher in SCLC with SVCT cohort (5.8 vs. 5, p < 0.001). Average income between the two cohort groups were similar. Medicaid and private insurance utilization were more common in SCLC with SVCT admissions compared to without SVCT. Patients presenting with SVC thrombosis had an increased hospital LOS (10 vs. 6 days, p < 0.001) and cost compared to other cohorts ($117,320 vs. $80,806, p < 0.005). All-cause mortality in patients with SCLC was 7.7% and the presence of SVC thrombosis significantly increased the odds of inpatient mortality (18.0%). Non-White races were associated with higher odds of mortality in SCLC admissions. In addition, patients with SVC thrombus also had greater odds of having a concomitant pulmonary embolism during hospitalization. Conclusions: In this study we found that race, insurance type, and comorbidities impacted the likelihood of developing thrombosis in the superior vena cava in patients with SCLC. Though the incidence is rare, SVC thrombosis indicates a poor prognostic factor for patients with SCLC. Further studies to evaluate these disparities in race and socioeconomic factors are warranted. The development of thrombosis and subsequent SVC syndrome is a potentially life-threatening condition; addressing potential reversible risk factors could improve mortality in a large subgroup of hospitalizations related to SCLC.
Role of consolidative thoracic and prophylactic cranial radiation in extensive stage small cell lung cancer in chemo-immunotherapy era.
Authors: Khatri Jai Kumar , Voland Rick , Flickinger John Charles , Tirona Maria Tria , Pacioles Toni , Dotson Jennifer , Jamil Muhammad Omer , Anwar Khurram , Yadala Vivek , Wright Thomas , DeCamp Malcolm , Shweihat Yousef , Zander Zani S , Cooper Mark Hayden , Varlotto John M. 
Published: June 2023

8595 Background: The role of consolidative thoracic and prophylactic brain radiation in extensive stage small cell lung cancer patients is controversial. We investigated the factors associated with the use of any radiation therapy (RT) and whether Radiation has a benefit to overall survival (OS) in the total patient group and whether this benefit is the same if Chemotherapy (CT) only is used, or chemo-immunotherapy (CT-IO) is used. Methods: The NCDB database was queried from years 2017-2019. Patients receiving systemic therapy- STX (CT or CT-IO) had to have at least 6 months of follow-up and have no brain metastases at diagnosis. All RT patients had to receive upfront systemic therapy, were treated 2 to 6 months from diagnosis, and if treated to the brain received 25Gy in 10 fractions only. Multi-variate analyses (MVA) were used to determine factors associated with OS and selection for any radiation. Propensity matching for factors affecting OS were used to generate Kaplan-Meier OS curves. Log-rank tests were used to determine differences in Kaplan Meier survival curves for the effects of RT on OS. Results: The total number of patients receiving RT or systemic therapy alone as well as their median follow-ups(months(mn) were (981, 33.02mn) and (8909, 30.59mn). The median time to the start of STX and RT were 22days and 135 days respectively. MVA noted that RT had a greater effect on OS (Thoracic, Brain, Both – HRs = 0.78, 0.75, and 0.68) than other interventions including IO (HR 0.87) and palliative care without RT (HR 1.07). Selection for radiation depended significantly upon factors affecting OS(HR) including liver metastases (0.59), females (1.21), age/10yr(0.78) and Charlson co-morbidity index of > 3(0.66), but did not depend upon insurance status, race, or county income/high school graduation rates. Propensity score matched OS curves noted the same effects of RT on OS whether CT or CT-IO was given. The lowest HRs were noted when both thoracic and brain RT were given (see table). Conclusions: The patient with extensive stage small cell lung cancer who reach candidacy and receive RT may have a significant improvement in OS compared to the patients treated only with CT or CT-IO. Combined thoracic and prophylactic brain RT seems to be better than either one alone. The impact of radiation whether given to one or two sites may be more beneficial than immunotherapy added to chemotherapy. [Table: see text]
Safety and preliminary efficacy of YK-029A, a novel EGFR TKI, in patients with advanced NSCLC harboring ex20ins, T790M or rare mutations.
Authors: Duan Jianchun , Zhao Jun , Zhang Li , Liu Baogang , Ren Xiubao , Li Mingjun , Shen Bo , Miao Liyun , Dai Xiumei , Pan Yueyin , Li Yupin , Yao Yu , Yang Kunyu , Wu Lin , Zhou Chengzhi , Yu Qitao , Xie Yanyan , Zeng Shan , Wang Jie ,   YK-029A-ASCO Authors' Group
Published: June 2023

9014 Background: This study aimed to evaluate the safety and preliminary efficacy of YK-029A, a novel third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, in treated or untreated patients with advanced NSCLC. Methods: This dose-escalation and dose-expansion phase 1 trial recruited previously untreated or treated patients with EGFR ex20ins mutant locally advanced or metastatic NSCLC and previously treated patients with EGFR T790M or rare mutations. In dose-escalation phase, patients with EGFR T790M mutation were enrolled. YK-029A was given at doses of 50, 100, 150, 200 to 250 mg/day (3+3 design). In dose-expansion phase, patients with EGFR T790M, EGFR ex20ins, or rare mutations were enrolled. The primary objective was safety. Dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) were explored. In the treatment-naïve cohort of EGFR ex20ins mutant NSCLC, patients were administered oral YK-029A 200 mg once daily in a 28-day cycle, and efficacy was assessed by the independent review committee. The study was registered (chinadrugtrials.org.cn,CTR20180350). Results: A total of 108 were included in the safety analysis set. DLT did not occur in dose-escalation phase. MTD was not reached. Treatment-emergent adverse events (TEAEs) of any grade and grade≥3 occurred in 106 (98.1%) and 41 (38.0%) patients, respectively. Treatment-related adverse events (TRAEs) of any grade and grade≥3 occurred in 102 (94.4%) and 30 (27.8%) patients, respectively. One patient had liver abscess related to YK-029A and died. Three patients terminated the treatment because of TEAEs. The most common TRAEs were diarrhea (46.3%), anemia (38.0%), and rash (32.4%). For the treatment-naïve EGFR ex20ins mutant cohort, 26 patients were included in the efficacy analysis set. Most patients were adenocarcinoma (96.4%) and at stage IV (85.7%). At the cut-off date on October 30, 2022, 19 patients (73.1%) had partial remission, five patients (19.2%) had stable disease, and two patients (7.7%) developed disease progression. The confirmed objective response rate achieved 73.1% (95% confidence interval [CI], 52.21% to 88.43%). The median progression-free survival was 9.3 months (95% CI, 5.85 to not evaluated). Conclusions: YK-029A was well tolerated and showed preliminary efficacy in treatment-naïve EGFR ex20ins mutant patients with locally advanced or metastatic NSCLC. [Table: see text]
Impact of EML4-ALK fusion variant and co-occurring TP53 mutation on treatment duration of first-line next-generation ALK TKIs in ALK fusion+ NSCLC.
Authors: Parikh Kaushal , Dimou Anastasios , Leventakos Konstantinos , Wan Yin , Lin Huamao Mark , Vincent Sylvie , Elliott Jennifer , Bonta Ioana R 
Published: June 2023

9029 Background: Molecular biomarkers such as EML4-ALK fusion variant 3 (V3) and TP53 mutation are associated with poor prognosis in patients (pts) with anaplastic lymphoma kinase fusion positive ( ALK+) non–small cell lung cancer (NSCLC). We evaluated the effect of EML4-ALK fusion variants and TP53 mutation status on time to treatment discontinuation (TTD) of first-line (1L) treatment with a next-generation ALK tyrosine kinase inhibitor (TKI) in pts with ALK+ NSCLC in the real-world setting. Methods: Pts with advanced/metastatic NSCLC who were ALK+ in circulating tumor DNA by Guardant360 (G360) liquid biopsy test from Jan 1, 2018, to Dec 31, 2021, and received 1L monotherapy with a next-generation ALK TKI (alectinib, brigatinib, ceritinib, lorlatinib) were identified in the Guardant INFORM clinical-genomics database. Median TTD of 1L ALK TKI treatment was determined by Kaplan-Meier (KM) methods. The impact of EML4-ALK fusion variant and TP53 mutation status on TTD was evaluated. Results: Database search identified 495 pts with advanced/metastatic NSCLC who had ALK fusion by G360; of these, 214 pts received 1L treatment with a next-generation ALK TKI; 164 had G360 testing before treatment (alectinib, n=147; brigatinib, n=7; ceritinib, n=2; lorlatinib, n=8). Among these 164 pts, median age was 58.6 y, 53% were female, and 29% had baseline brain metastases. Median follow-up from start of 1L treatment was 14.8 mo. Median TTD was 19.6 mo (95% CI: 13.6–not reached [NR]). TP53 mutations were detected in 66 pts (40%). Median (95% CI) TTD in pts with TP53 mutation vs WT was 17.1 (9.5–28.5) vs 21.9 mo (14.3–NR; log-rank P=0.1712). Of 130 pts with EML4-ALK fusion variant type detected, 63 (48%) had V1, 54 (42%) V3, 8 (6%) V2, 4 (3%) V5, and 1 (1%) V8. In pts with EML4-ALK fusion V1 vs V3, median (95% CI) TTD was 19.0 (13.6–NR) vs 21.8 mo (8.7–NR; HR: 0.73; log-rank P=0.3039), with the KM plot showing numerically longer TTD in pts with V1 vs V3 during the first 18 mo and lines crossing at the tail end. Of 117 pts with both an EML4-ALK fusion variant (V1/V3) and TP53 data, 21 (18%) had both V3 and a TP53 mutation. Pts with co-occurring EML4-ALK V3 and TP53 mutation had the shortest TTD (median TTD 8.7 [3.9–NR; HR: 2.59; P=0.0219]; Table). Conclusions: Among pts with NSCLC and ALK fusion, co-occurrence of EML4-ALK V3 and TP53 mutation is common and associated with poor prognosis and high risk of early discontinuation of 1L treatment with a next-generation ALK TKI, most likely due to disease progression. Additional novel or combination therapies are warranted for this subpopulation. [Table: see text]
Efficacy and safety of polymeric micelle paclitaxel (pm-Pac) plus tislelizumab and carboplatin for first-line treatment of patients with advanced squamous non-small-cell lung cancer.
Authors: Shi Meiqi , Zhao Yufang , Wang Li , Peng Wei , Zhu Xiangzhi , Li Xingwang , Wang Lv-hui , Ma An-mei , Tang Yi-qun 
Published: June 2023

9036 Background: The pm-paclitaxel formulation for injection (pm-Pac), a novel drug delivery system composed of nanoparticle-encapsulated paclitaxel micelles, combined with cisplatin has been proven to improve clinical outcomes in patients with advanced non-small-cell lung cancer (NSCLC). But the efficacy and safety of pm-Pac in addition to PD-1/PD-L1 inhibitors had never been reported before. Methods: Treatment-naive, stage IIIB/IV Sq-NSCLC patients with ECOG PS 0-2(≤1, 91.1%) were eligible. Participants were given intravenous Tislelizumab (200mg, d1) plus pm-Pac (230 mg/m2, d1) and carboplatin (AUC 5, d1), every 3 weeks until progression or unacceptable toxicity, with local radiotherapy or surgery allowed if treatment needed. The primary endpoints were ORR and safety. The secondary endpoints include DCR, PFS, and OS. AEs were graded according to CTCAE v5.0. Results: From Nov 2021 to Dec 2022, 45 patients were enrolled. The median age was 68 years (range 41-84), and most were male (93%) and former/current smokers (87%). 3 patients had baseline brain metastases and 31 patients had baseline PD-L1 evaluated. Twenty-two patients (48.9%) received subsequent local treatment because of the stable efficacy, including 18 radiotherapy and 4 surgery. Among all, 2 achieved confirmed CR, 36 achieved PR, 7 achieved SD, ORR was 84.4% and DCR was 100%. PFS and OS were immature. Kaplan-Meier survival analysis indicated that the 6m-PFS rate was 94.8% (95%CI:89.8%，97.6%), and a total of 41 (91.1%) patients are still alive on 1L treatment at the last follow-up on Feb 2023.The most common TRAE were alopecia (91.1%), leukopenia (80%), peripheral neurosensory numbness (55.6%) and extremity pain (24.4%). The most common grade 3 or higher AE was neutropenia (33.3%), which is commonly associated with chemotherapy. Conclusions: This is the first report about the new chemo-drug pm-Pac plus PD-1 inhibitor regimen that significantly improved ORR for advanced Sq-NSCLC with a tolerable safety profile, supporting further development of this new combination in the first-line treatment. Response rates. [Table: see text]
Prognostic and predictive implications of plasma ctDNA in guiding first-line targeted therapy for metastatic HER2-mutant non-small cell lung cancer (NSCLC).
Authors: Liu Si-Yang , Jee Justin , Santini Fernando Costa , Schoenfeld Adam Jacob , Eichholz Jordan , Johnson Kaylie , Martinez Andres , Guo Jiannan , Riaz Nadeem , Lee Nancy Y. , Pike Luke Roy George , Scher Howard I. , Drilon Alexander E. , Arcila Maria E. , Reis-Filho Jorge S. , Razavi Pedram , Jones David Randolph , Rudin Charles M. , Isbell James M. , Li Bob T. 
Published: June 2023

9052 Background: Trastuzumab deruxtecan (T-DXd) is the first HER2-targeted drug approved for NSCLC with human epidermal growth factor receptor 2 ( HER2, ERBB2) mutation in the second or later line settings. However, the optimal first-line treatment for these patients remains unclear. Access to rapid tissue sequencing is not always available, thus presenting challenges to first-line drug development. Circulating tumor DNA (ctDNA) analysis has the potential to overcome these obstacles to guide optimal first-line targeted therapy for patients with HER2-mutant NSCLC. Methods: We retrospectively analyzed patients with metastatic HER2-mutant NSCLC who underwent prospective clinical ctDNA sequencing at Memorial Sloan Kettering Cancer Center (MSK) from January 2016 to September 2022. HER2 mutations were identified by next-generation sequencing through MSK-IMPACT, MSK-ACCESS or Resolution ctDx Lung. Results: We identified 64 patients with metastatic HER2-mutant NSCLC who had received at least one line of systematic therapy. The median age was 63 years (range: 23–90), and there were more women (n = 38, 60%), and never-smokers (n = 38, 60%). The activating HER2 mutations included exon 20 insertions (73%), exon 8 (11%), 19 (11%), and 20 SNVs (5%). Plasma ctDNA was tested before initial therapy in 40 patients with a median overall survival (OS) of 28 months (95% CI 21-34), in whom 31 patients (78%) had at least one detectable ctDNA alteration by MSK-ACCESS and ctDx Lung. 55% (17/31) received chemoimmunotherapy with pembrolizumab as the first-line treatment. The median time to treatment discontinuation (TTD) was 6 months (95%CI 5.5-6.9). Additionally, 19% of patients (6/31) received a HER2-targeted antibody-drug conjugates (ADC) as first-line treatment with a median TTD of 6 months (95% CI 2-10), including 5 with T-DM1 and one who received first-line T-DXd treatment with a TTD of 9 months. Patients with baseline ctDNA alterations had significantly shorter OS (hazard ratio (HR), 5.25; 95% CI, 1–24; p = 0.019). Conclusions: Baseline plasma ctDNA has the potential to guide first-line targeted therapy for patients with HER2-mutant NSCLC. As an independent negative prognostic biomarker, detectable ctDNA at baseline would need to be taken into account for patient selection in future studies to avoid underestimating the effects of therapy.
Treatment patterns and unmet need for patients with advanced non-small cell lung cancer and poor performance status: A real-world evidence study.
Authors: Liu Stephen V. , Sussell Jesse , Boudreau Denise , Schuldt Robert , Harton Joanna , Bara Ilze , Pregenzer An , Porter Jason 
Published: June 2023

9077 Background: Performance Status (PS) is prognostic for poorer survival in oncology. Poor PS (pPS) may lead to inferior outcomes both as an independent factor and by limiting the range of available treatment options and the ability of patients to tolerate those regimens. Despite high real-world prevalence, patients with pPS are consistently underrepresented in clinical trials. Limited information is available regarding current treatment patterns for patients with pPS and advanced or metastatic non-small cell lung cancer (mNSCLC). Methods: We conducted a retrospective analysis using the nationwide de-identified Flatiron Health electronic health record (EHR)-derived database, selecting patients with mNSCLC diagnosed between 2017-2022 without EGFR or ALK genomic tumor aberrations. We estimated the prevalence of pPS (ECOG 2-3) within this cohort, and described common systemic treatment patterns by year and by PD-L1 status. For the subset of patients treated with pemetrexed/pembrolizumab/carboplatin (PPC), we estimated the association between pPS versus good PS (gPS - 0/1) and early discontinuation ( < 4 cycles) or dose reduction (AUC < 4) of carboplatin using logistic regression controlling for observable confounders. Results: One quarter (24%) of the 22,575 patients in our sample had pPS. Relative to patients with gPS, patients with pPS were more likely to be older (mean age 72 vs. 69y, p < 0.001), to have stage IV cancer (62% vs 56%, p < 0.001) and less likely to have known PD-L1 status (60% vs. 63%, p = 0.002). The fraction of patients with no documented treatment was substantially higher among pPS versus gPS (37% vs. 21%). In the subset of patients with PS3, 53% of patients had no documented treatment. The most common treatment regimens among pPS patients were mono-immunotherapy (mono-IO - 19%) and PPC (15%). Use of mono-IO was positively correlated with higher PD-L1 expression (44% vs. 14% vs. 5.9% in PD-L1 high/low/negative, respectively). No documented treatment was negatively correlated with PD-L1 status (26% vs. 35% vs. 42%). Among patients with PS3, higher rates of no documented treatment were observed (39% vs. 50% vs 58% for PD-L1 high/low/negative, respectively). Anti-CTLA-4 combination use was low regardless of PS. pPS was associated with greater likelihood of early carboplatin discontinuation, (adjusted odds ratio, aOR 2.06), and dose reduction (aOR 1.75), both p < 0.001. Conclusions: One quarter of patients with mNSCLC have pPS. These patients are almost twice as likely to receive no treatment as those with gPS, and within the subset treated with the most common platinum containing regimen (PPC), pPS patients are also more likely to both initiate carboplatin at a reduced dose, and to discontinue it prior to completion. This suggests a substantial unmet need for this important subset of patients with mNSCLC.