bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outcomes of anti-PD-(L1) therapy in combination with chemotherapy versus immunotherapy (IO) alone for first-line (1L) treatment of advanced non-small cell lung cancer (NSCLC) with PD-L1 score 1-49%: FDA pooled analysis.
Authors: Akinboro Oladimeji , Vallejo Jonathon Joseph , Mishra-Kalyani Pallavi Shruti , Larkins Erin A. , Drezner Nicole Lauren , Tang Shenghui , Pazdur Richard , Beaver Julia A. , Singh Harpreet 
Published: June 2021

9001 Background: IO + chemotherapy ± anti-angiogenics comprise FDA-approved 1L regimens for metastatic NSCLC, with IO-only therapy approved only for PD-L1-positive NSCLC. Patients with PD-L1 scores 1-49% have many therapeutic options, and little is known about how subgroups of patients experience benefit across treatment regimens. Methods: Data was pooled from 8 randomized controlled trials investigating anti-PD-(L)1 therapy as IO-only or in chemo-IO regimens for the 1L treatment of patients with advanced NSCLC. PD-L1 score was defined as the proportion of tumor cells stained by the assay, and analysis was conducted for patients whose tumors had PD-L1 score 1-49%. Tumor-infiltrating immune cell staining was not considered. OS and PFS were compared between chemo-IO and IO alone via a pooled analysis. Median survival times were estimated using Kaplan-Meier methods. Hazard ratios were estimated using Cox proportional hazards models stratified by trial and adjusted for age, sex, race, ECOG, histology and smoking status. Results: A total of 2108 patients with NSCLC and PD-L1 score 1-49% were identified for this analysis. Baseline characteristics were: 37% aged 65-74 years and 12% aged ≥75; 67% male; 79% white; 65% ECOG ≥ 1; and 85% smokers. Median follow-up was 12.1 months. This pooled analysis showed that patients receiving chemo-IO (N=639) had longer PFS and OS compared to patients treated with IO alone (N=529), with median PFS 7.7 vs 4.2 months (HR 0.60; 95% CI 0.48, 0.76) and median OS 21.4 vs 14.5 months (HR 0.68; 95% CI 0.52, 0.90). All results presented are considered exploratory and hypothesis generating. Conclusions: This exploratory pooled analysis suggests that chemo-IO may improve efficacy outcomes over IO alone in most subgroups of patients with advanced NSCLC with PD-L1 score 1-49%. Patients 75 and over experienced similar outcomes across therapeutic options.[Table: see text]
Overall survival and exploratory subgroup analyses from the phase 2 CodeBreaK 100 trial evaluating sotorasib in pretreated KRAS p.G12C mutated non-small cell lung cancer.
Authors: Skoulidis Ferdinandos , Li Bob T. , Govindan Ramaswamy , Dy Grace K. , Shapiro Geoffrey , Bauml Joshua , Schuler Martin H. , Addeo Alfredo , Kato Terufumi , Besse Benjamin , Anderson Abraham , Ang Agnes , Ngarmchamnanrith Gataree , Tran Qui , Velcheti Vamsidhar 
Published: June 2021

9003 Background: In the registrational phase 2 CodeBreaK 100 trial, sotorasib demonstrated an objective response rate (ORR) of 37.1% (95% Cl: 28.6, 46.2) and a median progression-free survival (PFS) of 6.8 months (95% Cl: 5.1, 8.2) in patients with pretreated KRAS p.G12C mutated non-small cell lung cancer (NSCLC). Tumor response was observed in patients bearing co-mutations in STK11, a driver of poor clinical outcomes with standard of care. Here, we report efficacy across an extended set of patient subgroups by key baseline characteristics and biomarkers. Methods: Sotorasib was given orally at 960 mg once daily to eligible patients who had advanced NSCLC harboring KRAS p.G12C and received prior standard therapies. Primary endpoint was ORR assessed by central review. Key secondary endpoints included PFS, overall survival, and safety. KRAS p.G12C mutant allele frequency (MAF) and tumor mutational burden (TMB) were analyzed by next-generation sequencing (NGS) using tissue samples. Mutational status of individual genes was determined by NGS using tissue and/or plasma samples. Correlations between response and KRAS p.G12C MAF, TMB, or co-mutations were analyzed in subsets of patients who had available respective results. Association between MAF and response was reported by odds ratio (95% CI), from a logistic regression with dependent variable of log odds of being a responder and an independent variable of MAF in a unit of 10%. Results: ORR across subgroups is presented in the Table. Response was independent of KRAS p.G12C MAF in the study population (odds ratio [95% CI]: 1.11 [0.88, 1.39]). OS remained immature. Conclusions: In the exploratory analyses of the phase 2 CodeBreaK 100 trial, the clinical benefit of sotorasib was observed across patient subgroups. Overall survival and updated exploratory analyses will be presented. Clinical trial information: NCT03600883. [Table: see text]
Racial disparities in biomarker testing and clinical trial enrollment in non-small cell lung cancer (NSCLC).
Authors: Bruno Debora S. , Hess Lisa M. , Li Xiaohong , Su Eric Wen , Zhu Yajun Emily , Patel Monaliben 
Published: June 2021

9005 Background: Cancer racial disparities may exist at many levels in the health care system, from screening to timely diagnosis and treatments received, as well as clinical trial enrollment. This study investigated differences in black versus white race among patients with NSCLC undergoing biomarker testing and clinical trial enrollment in the US. Methods: This retrospective observational study utilized the Flatiron Health database, which includes longitudinal data of patients with advanced/metastatic NSCLC. Patients were eligible if they had evidence of systemic therapy in the database from 1/1/2017 through 10/30/2020. Descriptive analyses summarized differences by race in biomarker testing and trial enrollment. Multivariable regression examined the relationship between these factors. Results: A total of 14,768 patients were eligible: 9,793 (66.3%) were white and 1,288 (8.7%) were black. 76.4% of white patients and 73.6% of black patients underwent at least one single molecular test or comprehensive genomic analysis (p = 0.03). Next-generation sequencing (NGS) was performed among 50.1% of white patients and 39.8% of black patients (p < 0.0001. Trial participation was observed among 3.9% of white and 1.9% of black patients (p = 0.0002). There was a statistically significant association between race (white vs black) and both biomarker testing (ever vs never) and trial participation (yes vs no) (both p < 0.001, unadjusted chi square). Differences in NGS testing, baseline biomarker testing, and race were retained as statistically significant (p < 0.01) in adjusted regression analyses. The receipt of first-line targeted therapy was comparable between white and black patients (10.2% and 9.2%, respectively, p = 0.24); however, this summary did not consider biomarker test results. First line use of pembrolizumab+carboplatin+pemetrexed was observed among 19.8% of white and 22.6% of black patients; carboplatin+paclitaxel was observed among 16.5% and 18.6%, and single-agent pembrolizumab was observed among 14.8% and 11.5%, respectively. Conclusions: The use of NGS-based testing, which is recommended by the National Comprehensive Cancer Network Clinical Guidelines in Oncology for patients with advanced/metastatic NSCLC, is the most notable disparity among black patients, with more than a 10 percentage-point difference in receipt of this testing versus white counterparts. This may in part contribute to the more than double the rate of participation in clinical trials observed among white patients, as many second line and beyond trials utilize molecular targets as inclusion criteria. While multiple factors are known to impact health care disparities, access to and receipt of appropriate biomarker testing may be an attenable goal in order to ensure equal access to quality care.
Clinical outcomes for plasma-based comprehensive genomic profiling versus tissue testing in advanced lung adenocarcinoma.
Authors: Page Ray D. , Drusbosky Leylah , Dada Hiba I. , Raymond Victoria M. , Daniel Davey B. , Divers Stephen G. , Reckamp Karen L. , Villalona-Calero Miguel Angel , Odegaard Justin Iver , Lanman Richard B. , Papadimitrakopoulou Vassiliki , Leighl Natasha B. 
Published: June 2021

9027 Background: Somatic genomic testing is recommended by numerous expert guidelines to inform targeted therapy treatment for patients with advanced lung adenocarcinoma (aLUAD). The NILE study was a prospective observational study that demonstrated non-inferiority of cell-free circulating tumor DNA (cfDNA)-based tumor genotyping compared to tissue-based genotyping to find targetable genomic alterations in patients with newly diagnosed aLUAD. As the cohort has matured, clinical outcomes data can now be reported. Methods: This prospective, multicenter North American study (NCT03615443) enrolled patients with previously untreated aLUAD who had standard of care (SOC) tissue genotyping performed and concurrent comprehensive cfDNA analysis using the commercially available Guardant360 assay (Guardant Health, Redwood City, CA). After 12 months of study enrollment, objective response rates, disease control rate, and time to treatment data were collected for patients with targetable genomic alterations, as defined by NCCN guidelines, who were treated with physician’s choice of therapy. Results: Among 282 patients on the study, 89 (31.6%) had an actionable biomarker detected by tissue (21.3%) and/or cfDNA (27.3%) analysis. Sixty-one (68.5%) of these patients were treated with an FDA-approved targeted therapy guided by somatic genotyping results ( EGFR, ALK, ROS1). Thirty-three patients were eligible for clinical response evaluation and demonstrated an objective response rate of 58% and disease control rate of 94%. Twenty-five (76%) achieved a durable response > 6 months; 17 (52%) achieved a durable response > 12 months. Patients responded to targeted therapy regardless of the variant allele frequency of the target alteration. The time to treatment (TtT) was significantly faster for cfDNA-informed biomarker detection as compared to tissue genotyping (median 18 vs 31 days, respectively; p = 0.0008). Conclusions: This is the first prospective community-based study to find that cfDNA detects guideline-recommended biomarkers at a rate similar to tissue genotyping, and therapeutic outcomes based on plasma-based comprehensive genomic profiling are comparable to published tissue-based targeted therapy clinical outcomes. The NILE study complements and confirms findings in the prospective FLAURA and SLLIP studies, which exclusively enrolled at academic sites. Clinical trial information: NCT03615443.
Second-line nintedanib plus docetaxel for patients with lung adenocarcinoma after failure on first-line immune checkpoint inhibitor combination therapy: Initial efficacy and safety results from VARGADO Cohort C.
Authors: Grohé Christian , Wehler Thomas , Dechow Tobias , Henschke Sven , Schuette Wolfgang , Dittrich Ina , Hammerschmidt Stefan , Müller-Huesmann Harald , Schumann Christian , Krüger Stefan , Atz Judith , Kaiser Rolf 
Published: June 2021

9033 Background: The treatment landscape in advanced non-small cell lung cancer (NSCLC) has undergone significant changes, with immune checkpoint inhibitor (ICI) +/- chemotherapy now the preferred first-line (1L) regimen for metastatic, non-mutated NSCLC. However, only limited clinical data are available to guide subsequent treatment selection. Nintedanib (Vargatef), an oral triple angiokinase inhibitor targeting the vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), and fibroblast growth factor receptor (FGFR) pathways, is approved in the EU and other countries in combination with docetaxel for the treatment of advanced adenocarcinoma NSCLC after failure on 1L chemotherapy. Methods: This analysis is part of the ongoing, prospective, non-interventional VARGADO study (NCT02392455) of nintedanib + docetaxel. Here, we present initial efficacy and safety results from 100 patients (pts) with adenocarcinoma NSCLC in Cohort C, who received second-line (2L) nintedanib + docetaxel after failure on prior 1L ICI in combination with chemotherapy. Results: In Cohort C, the median age was 63 years (range: 43–84); 58 pts (58.0%) were men, and 71 pts (71.0%) had ECOG PS 0/1. Ninety-five pts (95.0%) had received prior 1L pembrolizumab-based combination therapy. Thirty-nine pts (39.0%) had progressed within 6 months after the start of 1L therapy, and 66 pts (66.0%) had progressed within 9 months. Objective response rate with 2L nintedanib + docetaxel was 37.3% (22/59 pts), disease control rate was 67.8% (40/59 pts), and median progression-free survival (PFS) was 4.4 months (95% confidence interval [CI]: 2.6–6.6). Among pts who had experienced disease progression < 9 months after the start of 1L therapy (n = 66), median PFS from the start of 2L nintedanib + docetaxel was 4.1 months (95% CI: 2.5–6.6). Among pts with disease progression ≥9 months after the start of 1L therapy (n = 34), median PFS from the start of 2L nintedanib + docetaxel was 8.5 months (95% CI: 2.4–not estimable). Grade ≥3 treatment-emergent adverse events (TEAEs), serious TEAEs, and TEAEs leading to treatment discontinuation were observed in 47 pts (47.0%), 37 pts (37.0%) and 28 pts (28.0%), respectively. Conclusions: Initial data from VARGADO Cohort C provide the first evidence that 2L nintedanib + docetaxel has encouraging and clinically meaningful efficacy, and a manageable safety profile in pts with advanced adenocarcinoma NSCLC following progression on 1L ICI in combination with chemotherapy. Clinical trial information: NCT02392455.
Complete metabolic response in advanced non-small cell lung cancer patients with prolonged response to immune checkpoint inhibitor therapy.
Authors: Christoph Daniel Christian , Ferdinandus Justin , Metzenmacher Martin , Kessler Peter , Umutlu Lale , Aigner Clemens , Kambartel Karl-Otto , Grünwald Viktor , Eberhardt Wilfried Ernst Erich , Fendler Wolfgang Peter , Herrmann Ken , Faehling Martin 
Published: June 2021

9050 Background: Recently reported, extended follow-up data from KEYNOTE-024 or -010 indicates that non-small-cell lung cancer (NSCLC) patients can experience long-term benefit from immunotherapy irrespective of discontinuation (per protocol: 35 cycles ∼24 months) or type of response in computed tomography (CT). Similar results were observed in the pooled analysis of 5-year follow-up data from CheckMate-017 and -057. This raises the question, whether patients may safely discontinue immunotherapy after achieving durable response. However, recently published results from CheckMate-153 demonstrated inferior survival rates in patients ceasing immunotherapy after one year, therefore optimal treatment duration of immunotherapy in advanced NSCLC remains unknown. Protocols from published Phase-III trials implemented treatment for a period of approximately 24 months or until evidence of disease progression or unbearable toxicity. Therefore, the ideal duration of immunotherapy remains unclear, and finding markers of beneficial outcome is of great importance. Here, we determine the proportion of complete metabolic responses (CMR) in patients that have not progressed after 24 months of immunotherapy. Methods: This is a retrospective analysis of forty-five patients with positron emission tomography using 2-[18F]fluoro-2-deoxy-D-glucose (FDG-PET) imaging for assessment of residual metabolic activity after at least 24 months of immunotherapy. Lesion-uptake in FDG PET on or below background level (using mediastinum as reference) was considered as CMR. Time until best objective morphological response including disease stabilization was measured from start of immunotherapy until first stable CT-scan (i.e. no progression or further response compared to previous scan) using RECIST 1.1. Results: Out of 45 patients, 29 patients had a CMR (64%). CMR was observed more frequently in non-first line patients. Patients with CMR were younger (median 65.7 vs. 75.5, P = 0.03). Fourteen patients with CMR have discontinued therapy and have not progressed until time of analysis; however median follow-up was only 5.6 (range 0.8-17.0) months. Conclusions: After a minimum of 24 months of palliative immunotherapy for NSCLC, CMR occurred in almost two thirds of patients. Potentially, achievement of CMR might identify patients, for whom palliative immunotherapy may be safely discontinued.
Taletrectinib (AB-106; DS-6051b) in metastatic non-small cell lung cancer (NSCLC) patients with ROS1 fusion: Preliminary results of TRUST.
Authors: Zhou Caicun , Fan Huijie , Wang Yongsheng , Wu Huijuan , Yang Nong , Li KunYan , Wang Xicheng , Qin Xintian , Yu Qitao , Fang Yong , Tao Min , Meng Xue , Han Baohui , Dong Xiaorong , Yan Bing 
Published: June 2021

9066 Background: Taletrectinib (AB-106; DS-6051b) is a potent, selective ROS1/NTRK inhibitor. In two phase I trials, NSCLC patients (pts) with ROS1 fusion who received taletrectinib as first line ROS1 TKI had an objective response rate (ORR) of 66.7% (6/9) and median progression-free survival (PFS) of 29.1 mo (Sai-Hong Ignatius Ou et al., JTO Clinical and Research Reports, 2020). TRUST (NCT04395677) is an ongoing, multicenter, phase II study of taletrectinib in Chinese NSCLC pts with ROS1 fusion. Methods: The ROS1 TKI naïve or crizotinib pre-treated NSCLC patients with ROS1 fusion were treated with taletrectinib 400 or 600 mg QD. ROS1 testing was performed in each center and confirmed by central lab using RT-PCR. The primary endpoint was ORR (complete response [CR] + partial response [PR]) by IRC assessment. Secondary endpoints were disease control rate (DCR; CR + PR + stable disease), PFS and safety, etc. The pharmacokinetics (PK) of taletrectinib following 400 or 600 mg QD regimen was also evaluated. Results: As of the data cutoff (15 Jan 2021), 22 pts had received taletrectinib treatment. Median age was 54.5 years (range, 32-77 years;); 18.2% (4/22) had central nervous system metastases; ECOG performance status was 0 in 13.6% (3/22) of pts and 1 in 86.4% (19/22) of pts. Most pts (54.5%, 12/22) had prior systematic chemotherapy; 31.8% (7/22) of pts had prior crizotinib treatment. ORR by investigator among the crizotinib naïve pts with tumor assessment (N = 11) was 100% (95% CI, 72%-100%); 81.8% (18/22) of pts had treatment-emergent adverse events (TEAEs), including nausea, vomiting, diarrhea, transaminase elevation, white blood cell count decrease/neutrophil count decrease, etc. 13.6% (3/22) were grade ≥ 3, including fatigue (4.5%, 1/22), white blood cell decrease (4.5%, 1/22) and transaminase elevation (4.5%, 1/22).TEAEs led to dose interruption in 3 pts (13.6%), including dose reduction in 2 pts (9.1%). Taletrectinib in plasma approximately reached steady state on Cycle 1 Day 8 with 2- to 3- fold accumulations of exposure, which was consistent with results observed in the phase I trials. Conclusions: Taletrectinib demonstrated promising clinical activity with high ORR and good tolerability in ROS1 fusion positive NSCLC patients. The safety and PK profiles following taletrectinib treatment was generally consistent with the phase I trials. Clinical trial information: NCT04395677. Clinical trial information: NCT04395677.
CNS activity of poziotinib in NSCLC with exon 20 insertion mutations.
Authors: Le Xiuning , Garassino Marina Chiara , Cornelissen Robin , Socinski Mark A. , Tchekmedyian Nishan , Molina Julian R. , Baik Christina S , Leu Sharon , Dreiling Lyndah , Lebel Francois M. , Clarke Jeffrey Melson 
Published: June 2021

9093 Background: Treatment addressing non-small cell lung cancer (NSCLC) harboring EGFR or HER2 exon 20 insertion mutations remains an unmet need. These tumors are associated with a high incidence of CNS metastases and unfavorable survival rates. Poziotinib is a potent, irreversible, tyrosine kinase inhibitor (TKI) with a structure that can overcome the steric hindrance of the exon 20 limited binding pocket. Preclinical data suggest poziotinib CNS penetration, and here we show meaningful poziotinib CNS activity in patients with NSCLC harboring exon 20 insertion mutations in an ongoing multi-cohort, multi-center Phase 2 study (ZENITH20; NCT03318939). Methods: ZENITH20 enrolled previously treated and naïve patients with advanced/metastatic NSCLC and EGFR or HER2 exon 20 insertion mutations in several cohorts: Cohort 1 (C1) EGFR previously treated; Cohort 2 (C2) HER2 previously treated and Cohort 3 (C3) EGFR treatment-naïve. All patients with stable CNS metastases at baseline were included. Poziotinib (16 mg) was administered orally QD, with follow-up for up to 24 months. The primary endpoint was Objective Response Rate (ORR) evaluated centrally using RECIST v1.1 by an independent image review committee. Secondary endpoints included Disease Control Rate (DCR), Duration of Response (DOR), Progression-Free Survival (PFS) and safety. Primary efficacy results have been previously released. Intracranial response was determined based on the modified RECIST criteria. Results: A total of 284 patients across 3 cohorts (C1 n=115; and C2 n=90; and C3 n=79) with a median age of 60.5 years were enrolled. The median follow-up was 7.3, 8.3, and 9.2 months for all patients in C1, C2, and C3, respectively. In NSCLC patients that had baseline CNS lesions (N=36), the analysis showed a patient-based ORR of 22.2% (8/36) and a DCR of 88.9% (32/36). One patient in each cohort had a complete intracranial response and stable disease was 80.6% across 3 cohorts and 92.9% in C2. Two patients each in C1 and C3 had progressive disease (PD) and none had CNS progression in C2 (Table). Conclusions: Poziotinib exhibited clinically meaningful CNS activity in patients with EGFR or HER2 exon 20 mutations in ZENITH20 Cohorts 1-3. The majority of the patients had no CNS progression and 3/36 patients had intracranial complete responses. The preliminary data suggest that poziotinib may provide a meaningful treatment alternative for patients with NSCLC that harbor EGFR or HER2 exon 20 mutations and who present with CNS metastases that have poor prognosis. Clinical trial information: NCT03318939. [Table: see text]