bluuebunny/crossref_metadata_2025_split huggingface dataset:
Overall survival of adebrelimab plus chemotherapy and sequential thoracic radiotherapy as first-line treatment for extensive-stage small cell lung cancer.
Authors: Chen Dawei , Gao Aiqin , Zou Bing , Huang Wei , Shao Qian , Meng Xiangjiao , Zhang Pinliang , Tang Xiaoyong , Hu Xudong , Zhang Yan , Guo Jun , Zhao Wei , Fu Lei , Zhao Changhong , Yuan Jiajia , Yu Jinming , Wang Linlin 
Published: June 2024

8014 Background: The phase 3 trial (CAPSTONE-1) showed that adebrelimab (PD-L1 antibody) combined with first-line chemotherapy could prolong overall survival (OS) in patients (pts) with extensive-stage small cell lung cancer (ES-SCLC). Previous studies have shown that radiotherapy can enhance the immunogenicity of tumors, indicating the great potential of combining radiotherapy with immunotherapy. The purpose of this study was to explore the efficacy and safety of adebrelimab combined with chemotherapy and sequential thoracic radiotherapy (TRT) as first-line therapy for ES-SCLC. Methods: Key inclusion factors were 18-75 years old, histologically or cytologically confirmed ES-SCLC, ECOG performance status 0-1, no previous systematic treatment. Pts received 4~6 cycles of adebrelimab (20mg/kg, D1, q3w) combined with EP/EC (etoposide, 100mg/m2, D1-3, q3w and cisplatin, 75mg/m², D1, q3w or carboplatin, AUC = 5, D1, q3w). Pts with response sequentially received adebrelimab combined with consolidate TRT (≥30 Gy in 10 fractions or ≥50 Gy in 25 fractions, involved-field irradiation). Pts then entered the maintenance treatment stage with adebrelimab until disease progression or intolerable side effects. The primary endpoint was OS. The secondary endpoints included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and safety. Results: From October 2020 to April 2023, 67 pts with ES-SCLC were enrolled. Most patients were male (83.6%), current or former smokers (65.7%) with an ECOG performance status of 1 (95.5%). 22 (32.8%) patients were diagnosed with brain metastasis and 21 (31.3%) patients had liver metastasis at baseline. 45 patients received sequential TRT as planned. All patients were included in the safety and efficacy analysis population. At data cutoff (December 22, 2023), the median follow-up duration was 17.7 months. The median OS was 21.4 months (95% CI: 17.2–not reached months). 1-year and 2-year OS rate were 74.1% (95% CI: 63.6-86.4%) and 39.7% (95% CI: 25.5-61.9%). The median PFS was 10.1 months (95% CI: 6.9–15.5 months). The confirmed ORR was 71.6% (95% CI: 59.3-82.0%) and DCR was 89.6% (95% CI: 79.7-95.7%). The most common grade 3 or higher treatment-related adverse events included neutrophil count decreased (41.8%), white blood cell count decreased (19.4%) and lymphocyte count decreased (13.4%). No unexpected adverse events were observed. Conclusions: Adebrelimab plus chemotherapy and sequential TRT as first-line therapy for ES-SCLC showed promising efficacy and acceptable safety. Clinical trial information: NCT04562337 .
Multidimensional analysis of B7 homolog 3 (B7-H3) RNA expression in small-cell lung cancer (SCLC) molecular subtypes.
Authors: Gay Carl Michael , Owonikoko Taofeek K. , Byers Lauren Averett , Choudhury Noura J. , Ahmed Sajid , Cain Zachary , Qian Xiaozhong , Brentnall Matthew , Heeke Simon , Poi Ming , Wu Sharon , Rudin Charles M. 
Published: June 2024

8088 Background: SCLC is an aggressive cancer with a poor prognosis. B7-H3, a transmembrane protein showing low expression in normal tissues but overexpression in SCLC and other tumors, is a promising target for antibody–drug conjugates. We performed a multidimensional analysis of B7-H3/ CD276 expression in SCLC molecular subtypes (SCLC-A, -N, -P, and -I) and its relationship with expression of other immune-related genes. Methods: Clinical and molecular data for a cohort of patients (pts) with SCLC were derived from a real-world database (Caris Life Sciences, Irving, TX, USA). Tumor RNA expression was used to assign the SCLC molecular subtype derived from non-negative matrix factorization. Programmed death ligand-1 (PD-L1) protein expression was assessed by immunohistochemistry (IHC; antibody 22c3; positive cut-off: tumor proportion score >1%). Demographic, clinical, and molecular data were summarized by SCLC subtype or B7-H3 expression quartile (Q). Spearman’s r evaluated correlations between expression of B7-H3 and other immune-related genes/signatures. Results: The cohort included 1721 pts (52.5% female; 98.9% [434/439] smokers; median age, 67 years [range, 18–90+]). Across the subtypes, B7-H3 expression was high and remarkably consistent ( q>0.05; Table). Other biomarker genes, including DLL3 (q<0.05), had lower and more variable expression. Median (range) B7-H3 expression across all samples was 16.75 (0–68.2) transcripts per million (TPM). Across B7-H3 expression Qs, the proportion of PD-L1-positive pts by IHC was similar (Q1, 39.8%; Q2, 46.5%; Q3, 40.7%; Q4, 39.2%). Median (95% confidence interval) B7-H3 expression was similar between pts with prior immunotherapy ( n=24; 14.43 [11.64–21.17] TPM) and pts without ( n=208; 14.20 [13.00–15.91] TPM); treatment information was not available for the remaining samples in this cohort. B7-H3 expression was not strongly correlated with any other immune-related genes/signatures, although several had moderate correlation ( HAVCR2/ TIM3, r=0.59; PDCD1LG2/ PD-L2, r=0.56; M2 macrophages, r=0.56; CD86, r=0.56). Conclusions: In pts with SCLC, B7-H3 showed high and consistent expression across subgroups defined by molecular subtype or prior immunotherapy. The relative expression of B7-H3 was higher and less variable among molecular subtypes than for other key molecular targets in this tumor type, including DLL3. B7-H3 expression had limited association with PD-L1 expression, supporting a role as a distinct therapeutic target. [Table: see text]
PD-L1 and alternative immune checkpoints (AICs) in non-small cell lung cancer (NSCLC): Insights into the tumor immune microenvironment (TIME) and immunotherapy (IO) outcomes.
Authors: D'Aiello Angelica , Nazari Shayan , Jeon Hyein , Elliott Andrew , Vanderwalde Ari M. , Borghaei Hossein , Liu Stephen V. , Zang Xingxing , Halmos Balazs , Cheng Haiying 
Published: June 2024

8531 Background: PD-L1 and recently identified AICs (B7x, B7-H3, and HHLA2) may function as key immune evasion mechanisms in NSCLC and influence IO efficacy. This study explores the expression patterns of PD-L1 and AICs within the TIME and their impact on IO outcomes in NSCLC, including key molecular subtypes. Methods: NSCLC samples (n=27,629) were analyzed (Caris Life Sciences) with NextGen Sequencing on DNA (592 genes or whole exome)/RNA (whole transcriptome). Tumor cell PD-L1 expression (22c3) was assessed by IHC. Gene expression profiles were analyzed for IFN-γ score and QuantiSEQ was used to assess immune cell infiltration in the TIME. Real-world overall survival (rwOS: from time of biopsy to last contact), time on treatment [TOT: from the first pembrolizumab (pembro) treatment to the last], and OS on pembro (OSpem: from pembro start to last contact) were calculated. Mann-Whitney U, X2/Fisher-Exact, and log-rank tests were applied where appropriate. Results: PD-L1 IHC+ NSCLC and cases with high PD-L1 RNA expression had higher IFN-γ score and immune cell fractions (p<0.0001 for both) vs PD-L1 IHC- and low expression, respectively. Additionally, PD-L1 IHC+ NSCLC was associated with (a/w) higher median transcript levels (TPM) of PD-L1 and B7-H3, while PD-L1 IHC- NSCLC was a/w higher TPM of HHLA2 and B7x (p<0.0001 for all). AICs expression varied by molecular subtype, e.g., higher HHLA2/B7x RNA in EGFR mutant vs wild-type (WT) NSCLC. Moreover, PD-L1 IHC+ NSCLC and cases with high PD-L1 RNA and low B7H3 RNA were a/w longer rwOS, OSpem, and TOT; high HHLA2 RNA was a/w longer rwOS and OSpem with similar TOT; and low B7x RNA expression was a/w longer OSpem and TOT with similar rwOS (Table). Conclusions: Both PD-L1 IHC+ NSCLC and cases with high PD-L1 RNA expression are a/w a more inflammatory TIME, and superior survival and IO outcomes. Moreover, consistent with our prior HHLA2 IHC work (PMIDs: 27553831, 29374053), HHLA2 RNA expression was significantly higher in PD-L1 IHC- and EGFR mutant cases. These findings support the potential utility of transcriptomics along with protein expression for assessing novel predictive biomarkers for IO. Furthermore, the distinct expression profiles of AICs identified in our study may represent key subtypes mediating IO response in WT and EGFR mutant NSCLC. [Table: see text]
Molecular profiling across histologies in lung cancer: Time to change WHO nomenclature?
Authors: Russo Alessandro , Javey Manana , Hiemenz Matthew , Kaplan Benjamin G , Yaung Stephanie J. , Huang Richard S.P. , Rolfo Christian Diego 
Published: June 2024

8532 Background: Biomarker testing is essential for optimal therapeutic management of Non-Small lung Cancer (NSCLC). However, a not negligible percentage of patients (pts) is not tested in clinical practice for all the relevant actionable biomarkers. Biomarker testing is recommended in lung adenocarcinoma (LUAD), while in tumors with other histologies it is reserved when clinical features indicate a higher probability of an oncogenic driver. Histopathology report and biomarker testing are usually performed sequentially, which is time consuming and delays patient care. Herein we determined the distribution of actionable biomarkers across NSCLC histotypes and other clinic-demographic characteristics. Methods: This is an observational retrospective analysis on histologically confirmed NSCLC cases tested between 2014-2022 using FoundationOne/FoundationOneCDx assay. Histopathologies of all cases were centrally reviewed and confirmed by Board Certified Anatomic Pathologists. Results: 82,328 NSCLC pts were included. Actionable genomic alterations (GA) were found in 35.1% of the cases (Table). LUAD and adenosquamous (ASC) were more commonly associated with actionable GA (45.8% and 40.9%, respectively) as compared with sarcomatoid (29.1%), not otherwise specified (NOS) (27.6%), large cell (LCC) (21.1%), and squamous cell (LUSC) (6.5%) histologies. Sarcomatoid histology had the highest METex14 skipping mutations (muts) frequency (9.9% vs. 2.4% in LUAD). Tumor mutational burden (TMB) ≥10 Mut/Mb was associated with histology (50.9% in LCC, 40.8% in NOS, 39.1% in LUSC, and 36.3% in sarcomatoid vs. 31.2% in LUAD and 29.2% in ASC). Pts with actionable GA usually had a low TMB (80.9%). A significant correlation (p<0.005) between age and actionable GA was reported for BRAF/ ERBB2 muts, ALK/RET/ROS1 rearrangements (RE), and MET amplification. EGFR actionable muts and KRASG12C were more commonly observed in females, whereas no significant correlation between sex and other GA was observed. Finally, genetic ancestry analyses revealed a strong correlation between EGFR actionable muts and South/East Asian and American ancestries, but not for other GA. Conclusions: This is the largest NSCLC dataset analyzed for biomarker distribution across histologies, age, sex and genetic ancestry. This dataset confirms sufficient enough biomarker prevalence across LUAD and ASC carcinoma to be included in WHO nomenclature for lung tumors, and provides reassurance that cases with NOS, LCC and sarcomatoid histologies must be considered for biomarker workup. [Table: see text]
Socioeconomic disparities in survival outcomes of patients with NSCLC with brain metastases: A real-world analysis.
Authors: Bellur Shreyas S , Ahmad Shahzaib , Bhat Vivek , Ganiyani Mohammad Arfat , Ozair Ahmad , Jayram Diya , Khosla Atulya Aman , Podder Vivek , Ahluwalia Manmeet Singh 
Published: June 2024

8569 Background: Racial and ethnic disparities have been previously reported in outcomes of metastatic cancer patients. While novel therapies have improved outcomes of NSCLC patients with brain metastases (BM), however, barriers to therapy persist, warranting updated evaluations of socioeconomic disparities in clinical outcomes. Methods: A retrospective cohort study was conducted on patients diagnosed with NSCLC BM in 2018-2020 in the National Cancer Database. Patients were classified as White, Black, American Indian, Aleutian or Pacific Islander (AAPI), or Asian. Sociodemographic and clinical outcomes were analyzed and reported using median overall survival (mOS) (95% CI). Multivariate analyses were performed using Cox proportional hazard models adjusting for sex, race, facility type, and income and reported using hazard ratios for death (HR) (95% CI). Results: 13850 patients with NSCLC BM were included: 81% (N=11123) were White, 14% (N=1914) Black, 0.5% (N=73) AAPI, 3.7% (N=508) Asian. 8% were treated in community cancer centers (CCC) and 39% in comprehensive CCCs (CCCC). 55% were Medicare-insured and 30% had annual income >$74063. Compared to White, Asian patients had significantly better mOS of 29.1 months (24.57-36.5). Compared to non-Hispanic, Hispanic patients had significantly better mOS at 18.1 months (14.5-24.3). Medicaid and Medicare-insured had significantly worse outcomes vs. private-insured patients – mOS of 14.62 months (12.75-16.49) and 8.84 months (8.41-9.36) vs. 21.72 months (20.37-23.29). In multivariate analyses, compared to White, Asians had an HR of 0.61 (0.53-0.70). Hispanic had a HR of 0.77 (0.67-0.88) compared to non-Hispanic patients (P<0.05). Compared to academic centers, patients treated at CCC (HR 1.42 (1.29-1.57)) and CCCC (HR 1.25 (1.19, 1.32)) had worse outcomes. Patients with higher annual income (>$74063) had better outcomes compared to those with low income (<$46277) (HR 0.83 (0.78-0.89), P<0.002). Conclusions: Asian and Hispanic patients with NSCLC BM had better 3-year survival compared to White and non-Hispanic patients, respectively. Patients at community centers had worse outcomes than those at academic centers. Medicare-insured and Medicaid-insured patients had unfavorable outcomes. Targeted efforts are warranted to improve disparities in outcomes across racial and ethnic groups. [Table: see text]
A randomized phase II trial of 8 months of afatinib switching to osimertinib (A) versus osimertinib alone (B) as first-line treatment in advanced NSCLC patients with common EGFR mutation: YAMATO study (TORG1939/WJOG12919L).
Authors: Nakamura Atsushi , Yoshioka Hiroshige , Misumi Toshihiro , Yokoyama Toshihide , Itani Hidetoshi , Tachihara Motoko , Tanaka Kaoru , Akamatsu Hiroaki , Ono Akira , Ikeda Satoshi , Tokito Takaaki , Sato Yuki , Mori Masahide , Uemura Takehiro , Hata Akito , Hosokawa Shinobu , Ishikawa Hideki , Yamamoto Nobuyuki , Okamoto Hiroaki , Kurata Takayasu 
Published: June 2024

8574 Background: NSCLC with common EGFR mutation (L858R or exon 19 deletion (Del19)) is known to originally comprise small portion of uncommon and compound EGFR variant cells including T790M-mutant ones albeit treatment-naïve. To overcome concomitant heterogeneous EGFR mutations, we planned a randomized phase II trial to assess the strategy of switching to osimertinib following 8 months of afatinib compared with osimertinib alone. Methods: YAMATO study is an open-label, multi-center, randomized phase II study. Patients with newly diagnosed stage III/IV/recurrent NSCLC harboring EGFR activating mutations (L858R or Del19) were randomized in a 1:1 ratio to receive up-front 8 months of afatinib (30 mg or 40 mg QD) followed by osimertinib (80 mg QD) (arm A) or osimertinib (80mg QD) alone (arm B) until disease progression or intolerable toxicity. The primary endpoint is 2-year progression free survival (PFS) rate with threshold rate of 22% and expected rate of 40% (one-tailed alpha of 0.1, beta of 0.2). Secondary endpoints are objective response rate (ORR), PFS, time to treatment failure, overall survival and adverse events. Results: Between May 2020 and Apr 2021, 113 patients were enrolled from 27 institutions (A/B 56/57). Patient characteristics were as follows: median ages, 73.5/71 years (range 41-85/41-92 years); proportion of males, 42.9/35.1%; EGFR mutation types, L858R/Del19 59/41% in A, 58/42% in B. The difference of two-year PFS rate was not observed statistically significant between groups (37.3% [80% CI, 29.0 to 45.5] in arm A vs 47.4% [80% CI, 38.5 to 55.7] in arm B; p=0.44; HR:1.28 [80% CI, 0.95-1.73]). The ORR was 82% in arm A and 87% in arm B. With the median follow-up of 27.5 months, median PFS was 16.8 months in arm A, and 22.2 months in arm B (HR: 1.280, p = 0.29). Severe pneumonitis occurred in 7% in arm A, most of which developed after switching to osimertinib, and 1.8% in arm B. Conclusions: YAMATO study failed to demonstrate the superiority of EGFR-TKI switching therapy of 8 months afatinib to osimertinib over osimertinib alone in terms of 2-year PFS rate in untreated advanced NSCLC patients with common EGFR mutations. Clinical trial information: 031200021 .
A real-world study on biomarker retesting among patients with non-small cell lung cancer and disparity in outcomes.
Authors: Crawford Samuel , Aggarwal Charu , Ng Sophia , Xu Qingqing , Simmons Archana , Gulati Ashish , Beasley Mary Beth 
Published: June 2024

8590 Background: Prior studies revealed sociodemographic disparities in biomarker testing among patients (pts) with advanced/metastatic non-small cell lung cancer (a/mNSCLC). However, the association of testing disparities with clinical outcomes among real-world pts requires further characterization. Methods: This retrospective study used ConcertAI Patient360™ US dataset to assess biomarker testing disparities and their association with median overall survival (mOS) among adults with a/mNSCLC (2017–2022) who received ≥1 line of therapy with ≥90-day follow-up. Analyses were conducted in pts who initiated first-line (1L) treatment and stratified by setting (community vs academic) and race. Biomarker testing is a curated data element in this database, leveraging structured and unstructured electronic medical record data and includes the following biomarkers ALK, BRAF, EGFR, KRAS, MET amp, MET exon 14, NTRK, PD-L1, RET, and ROS1. Biomarker testing to inform 1L decision was defined as testing before 1L start. Testing to inform second-line (2L) decision was defined as testing after 1L start and before 2L start. Variables were compared using chi-square or ANOVA tests. Unadjusted and adjusted OS using multivariate Cox proportional hazards are reported. Results: Of 3678 pts included in the 1L cohort, 3127 (85%) received 1L testing. In community settings, 22% of Black pts vs 15% of White pts did not receive 1L testing (P=0.002), whereas 1L testing rates between races were similar in academic settings (Table). In 2L community setting among pts who received 1L but not 2L testing, mOS was 5.9 vs 9.9 months in Black (n=54) vs White (n=529) pts, respectively (P=0.35). In 2L community setting among pts who were and were not tested prior to 1L and not tested at 2L, mOS was 5.9 vs 10.1 months in Black (n=62) vs White (n=613) pts, respectively (P=0.27). Accounting for recorded sociodemographic and clinical characteristics at baseline, differences in OS by testing setting and status start to normalize to the reference group. Disparities within groups appear to potentially exist despite no statistical significance (except for ECOG score of 2+). Conclusions: Despite small 2L sample sizes and lack of significance, disparities in testing rates and outcomes were observed, which may be overcome by normalizing testing across race and treatment setting to potentially improve pt outcomes. Further analysis can be performed across census regions. Further research is needed to confirm the impact of lack of biomarker testing on pt outcomes on a broader scale, particularly around characteristics that may impact outcomes but were undetected in this dataset. [Table: see text]
Phase 1/2 trial of the XPO1 inhibitor selinexor in combination with docetaxel in previously treated, advanced KRAS mutant non-small cell lung cancer (NSCLC).
Authors: von Itzstein Mitchell S. , Burns Timothy F. , Dowell Jonathan , Horn Leora , Camidge David Ross , York Sally J. , Eaton Keith D. , Walker Christopher James , Zhang Song , Gerber David E 
Published: June 2024

8597 Background: KRAS mutant NSCLC remains a therapeutic challenge. Although KRAS G12C inhibitors are now approved for cases harboring that specific mutation, their efficacy is modest and the G12C variant accounts for only 40% of KRAS mutations in NSCLC. To date, there are no approved targeted therapies for non-G12C KRAS mutant NSCLC. Selective inhibitors of nuclear export (SINE) modulate cancer cell biology by retaining certain proteins—such as tumor suppressors—within the nucleus, where they remain physiologically active. The XPO1 inhibitor selinexor demonstrated efficacyinpreclinicalNSCLC models harboring various KRAS mutations. Methods: In this 3 + 3 dose-escalation phase 1/2 trial, patients with previously treated advanced KRAS mutant NSCLC received selinexor (dosed orally weekly) plus docetaxel 75 mg/m2 IV every three weeks (NCT03095612). Prior treatment with KRAS G12C inhibitors was permitted. Results: Among 40 enrolled patients, median age was 66 years, 22 (55%) were female, and 34 (85%) were white. KRAS mutation types included G12C (28%), G12V (23%), G12D (20%), G12A (13%), G12R (5%), G13C (5%), and one case each of G12S, G13D, Q61L, and K117N. Patients had received a median of 2 prior lines of therapy (range 1-4). The maximum tolerated dose of selinexor was 60 mg PO weekly combined with docetaxel. The most common adverse events (AE) were nausea (73%, Gr ≥3 8%), fatigue (70%, Gr ≥3 5%), neutropenia (65%, Gr ≥3 60%), diarrhea (58%, Gr ≥3 10%), anorexia (50%, Gr ≥3 0%), and vomiting (45%, Gr ≥3 5%). Of 32 patients evaluable for efficacy, 7 (22%) had partial response (PR) and 18 (56%) had stable disease (SD) as best response. Median progression-free survival (PFS) was 4.1 months (95% CI, 2.9-5 months); median overall survival (OS) was 7.1 months (95% CI, 4.5-13.7 months). Clinical outcomes did not differ significantly among KRAS mutation types. However, TP53co-mutations (48%) were associated with significantly worse outcomes: disease control rate (PR + SD) 27% vs 92% ( P=0.006); median PFS 1.8 vs 7.4 months ( P<0.001); median OS 5.8 vs 17 months ( P=0.006). Additional biomarker studies are ongoing. Conclusions: Selinexor plus docetaxel is tolerated with multi-agent supportive care. The combination shows moderate efficacy across KRAS mutation types, with promising activity in TP53 wild type cases. Clinical trial information: NCT03095612 .