bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of social determinants on overall survival in advanced-stage non-small cell lung cancer patients.
Authors: Bello Andreas , Makani Neeharika Srivastava 
Published: June 2021

e21117 Background: Non-small cell lung cancer (NSCLC) is the most prevalent form of lung cancer. Many studies have evaluated the association of social determinants with outcomes in early-stage NSCLC. These studies have shown statistically and clinically significant associations between overall survival (OS) and other social factors (e.g marital status, educational attainment). The aim of our study was to better understand the role of various social determinants of health (SDH) on OS in advanced-stage NSCLC patients in a community oncology practice in Florida. Methods: In this retrospective study, 125 patients with stage III and IV NSCLC were recruited between January 1st, 2014 until December 31st, 2018. We performed both categorical and continuous analyses (Pearson’s chi-square and Kruskal-Wallis test, respectively) to evaluate the association between median OS and several independent variables, including; gender, race, marital status, insurance status, living status, receiving financial assistance (FA), alcohol use, and smoking histories. OS is defined as the date of diagnosis up to the date of death. Other confounders that were analyzed included histology, treatment modality, comorbidities, and performance status of the patients. Results: Of the total study population (n = 125), 60% identified as male with a mean age of 73 years for the study population. The majority of patients (89%) identified as white; 56% were married, and 81% lived with someone. 66% of patients had an HMO insurance plan, and 51% of patients obtained FA to help with treatment care costs. 47% of patients identified as former smokers and 54% denied any alcohol use. The median OS for the patient population was 0.756 years. Chi-square analyses revealed that patients who received FA were more likely to live longer than median OS as opposed to patients that did not receive FA (OR = 2.41, 95% CI [1.18, 4.96], p = 0.050). Kruskal-Wallis analyses demonstrated that patients receiving FA had nearly a two-fold increase in median OS compared to patients without financial assistance (median OS = 1.01 years vs. 0.545 years, respectively; p = 0.013). However, other social determinants evaluated did not have a significant impact on relative OS in advanced-stage NSCLC. Conclusions: Ultimately, our study concludes that receiving FA has a significant association with increased OS in advanced-stage NSCLC patients. This study highlights the importance of reducing the financial burden of advanced-stage NSCLC patients and how FA impacts patient outcomes. Future prospective cohort studies with a larger sample size are warranted to identify other SDH, as well as the underlying mechanisms affecting median OS, in patients with advanced-stage NSCLC.
Association of progression free survival with the timing of genomic testing in non-small cell lung cancer: Evidence from the GuardantInform clinic-genomic database.
Authors: Hiatt Mark D. , Yu Junhua , Zhang Nicole , McNeal Amy , Kaylor Julie , Lang Kathryn 
Published: June 2021

e21143 Background: The clinical utility of ctDNA analysis for biomarker identification in advanced non-small cell lung cancer (NSCLC) has been established, supporting clinical adoption of this testing modality. All FDA-approved, immune-checkpoint inhibitor (ICI) immunotherapies require the prerequisite of negativity for ALK rearrangement and EGFR mutation, or prior toxicity or progression on oral therapies targeting mutations in these genes. Despite these recommendations and support from the American Society of Clinical Oncology and National Comprehensive Cancer Network, broad-panel marker testing for targeted therapy options in NSCLC continues to be underperformed. Data are even limited on when those tests are typically conducted and the effects of timing on the treatment outcomes. Methods: The GuardantINFORM™ clinic-genomic database was interrogated for patients over the age of 18 having a Guardant360 test positive for EGFR mutations of L858R or exon 19 after 2016 and known to have a confirmed diagnosis of lung cancer one year prior to testing. Patients had to have at least three claims prior to, and 90 days of follow-up after, their test. Patients were stratified into three groups by pre- and post-test treatment: 1) patients treated with an EGFR tyrosine kinase inhibitor (TKI) as a first-line treatment after the test, with no other chemotherapy, ICI immunotherapy (IO), or targeted therapy before the test; 2) patients with other first-line treatments prior to the test and then EGFR TKI immediately following the test; and 3) patients treated with ICI or chemotherapy after the test and before EGFR TKI or patients not treated after the test. Real-world time to next treatment (rwTTN) was defined as the index date to the treatment different than the index therapy. Progression free survival (PFS) time was defined as rwTTN or time to death, whichever came earlier. Patients who experienced adverse events (AEs) associated with chemotherapy or IO were reported as a percentage (p-value<0.001). Results: Among the 3 cohorts of patients (384 in each group who were matched on age with difference < 3, gender, and follow-up time with difference < 4 months) identified, a statistically significant difference in PFS was discovered between group 1 ( EGFR TKI as first-line treatment) and the other two groups based on the Cox proportional hazard model [hazard ratio=1.8, p-value<0.001, median survival time for group 1= 26 months (95% CI 23-29) vs. 17 months (95% CI 14-19)]. No difference existed in PFS between groups 2 and 3. The proportion of patients experiencing treatment-associated AEs was lowest in group 1 (13.5% vs 15.9% in group 2 vs 30.2% in group 3 for ICI-related AEs, 16.9% vs 23.2% vs 38.5% for chemo-related AEs, p-value<0.001). Conclusions: Performing genomic testing sooner, as early as first-line treatment, may improve the treatment response for patients with NSCLC.
Molecular testing in advanced lung adenocarcinoma: A single-center experience.
Authors: Khan Mahir , Nguyen Ryan Huu-Tuan , Pasquinelli Mary , Feldman Lawrence Eric 
Published: June 2021

e21157 Background: Standard of care testing prior to first-line therapy for advanced lung non-small cell lung cancer (NSCLC) includes EGFR mutations, ALK rearrangements, and PD-L1 expression. There is limited real-world evidence on NSCLC molecular testing patterns in underrepresented racial and ethnic populations. Methods: We identified adult patients newly diagnosed with stage IV lung adenocarcinoma at the University of Illinois Hospital & Health Sciences System between January 1, 2015 and October 1, 2019. Rates of biomarker testing for EGFR, ALK, and PD-L1 were determined, as well as the median time from tissue biopsy to each result. Data were stratified by race and ethnicity. Timelines of molecular testing were studied in relation to cancer therapy initiation. Results: Among 80 patients diagnosed with advanced NSCLC, 70 (87.5%) received EGFR testing, 69 (86.3%) received ALK testing, and 40 (50%) received PD-L1 testing from 2015-2019. Thirty-one (81.6%) patients diagnosed from 2017-2019 had PD-L1 testing. Median time from biopsy to molecular test result in the overall population was 3.0 weeks for EGFR, 3.0 weeks for ALK, and 2.0 weeks for PD-L1. There was no significant difference in EGFR and ALK testing rates between Black and non-Black patients. PD-L1 testing was decreased in Black patients compared to non-Black patients ( p = 0.02) from 2015-2019, but there was no significant difference from 2017-2019. All three biomarkers had similar testing rates between White and non-White patients and between Hispanic and non-Hispanic patients. Median time from biopsy to PD-L1 result decreased from over 12 weeks in 2015 and 2016 to 2 weeks in 2018 and 2019. Six (7.5%) patients received first-line treatment before results were available. Two (2.5%) required treatment changes based on results. Conclusions: In an urban, academic center we found similar EGFR and ALK testing rates among race and ethnicity subgroups. PD-L1 testing was lower in Black patients from 2015-2019 but not after national guidelines recommended PD-L1 testing in 2017. Treatment was initiated without full biomarker data in multiple cases, sometimes leading to changes in therapy after results were obtained. Further studies are indicated to determine strategies for comprehensive, timely, and equitable biomarker testing in advanced NSCLC.[Table: see text]
Efficacy of gefitinib combined with bevacizumab versus gefitinib in advanced EGFR L858R NSCLC.
Authors: Zhao Xinmin , Wu Xianghua , Wang Huijie , Yu Hui , Sun Si , Feng Yu , Wang Jialei 
Published: June 2021

e21185 Background: 60-80% of EGFR+ NSCLC could benefit from the treatment of EGFR TKIs. However, as a result of acquired resistance, median progression-free survival (PFS) associated with EGFR-TKIs monotherapy was rarely longer than 11 months. Vascular endothelial growth factor (VEGF) and its receptor (VEGFR) play an important role in the angiogenesis and progression of NSCLC. The combination of EGFR-TKIs and anti-vascular drugs that inhibit the EGFR and VEGF/VEGFR pathways may be a potential therapeutic option for EGFR-mutant NSCLC. The purpose of our study was to evaluate whether gefitinib combined with bevacizumab is associated with an increased PFS benefit compared with gefitinib alone. Methods: This study is a randomized, open-controlled, single-center study. A total of 43 advanced non-squamous NSCLC patients with EGFR L858R mutations were enrolled, including 24 in the experimental group and 19 in the control group. The experimental group received gefitinib combined with bevacizumab (gefitinib 250 mg, QD+bevacizumab 7.5 mg/kg, Q3W), and the control group received gefitinib monotherapy (250 mg, QD). Response to treatment was evaluated after one month of the treatment, followed by once every two months, and adverse events were graded. The primary endpoint was PFS, and secondary endpoints included objective response rate (ORR), disease control rate (DCR), duration of response (DOR), overall survival (OS), and safety and tolerability evaluation. Samples at baseline (tissue or liquid biopsy), 43 days after treatment (liquid biopsy), and disease progression were subjected to genomic (139-gene NGS panel) profiling. Results: As of December 31, 2020, 22 patients were evaluable (12 for experimental group, 10 for control group). The ORR of the experimental group and the control group were 42% vs 60%, respectively, with no significant difference (experimental group: CR = 0, PR = 5, SD = 7, PD = 0; control group: CR = 0, PR = 6, SD = 4, PD = 0). Main adverse reactions included skin rash (n = 16), diarrhea (n = 24), hypertension (n = 2), proteinuria (n = 1). Other special cases developed fever, nausea and vomiting, elevated platelets, conjunctivitis, back pain, which were manageable. 36 patients with baseline liquid biopsy samples can be evaluated (33 plasma and 3 pleural fluid samples). Of these, EGFR L858R were detectable in 86% (n = 31) of patients. The most common co-mutated gene was TP53 (57%), followed by DNMT3A (49%) and TET2 (17%). Mutation profiles were comparable between the two groups. Conclusions: Compared to gefitinib monotherapy, gefitinib combined with bevacizumab in the treatment of non-squamous NSCLC with EGFR L858R showed similar efficacy and safety profiles.
Residual of circulating tumor DNA (ctDNA) indicated therapeutic efficacy of sintilimab plus docetaxel in patients with previously treated advanced non-small cell lung cancer (NSCLC).
Authors: Wang Zhehai , Han Xiao , Guo Jun , Jia Ming , Zhu Changbin , Zhu Dongyuan , Zhang Xiqin , Tang Xiaoyong , Meng Xiangjiao 
Published: June 2021

e21207 Background: The synergetic effect of ICIs plus chemotherapy has been demonstrated in first line setting for patients with advanced NSCLC. As previously reported, sintilimab plus docetaxel in advanced Chinese NSCLC pts who had failed first-line chemotherapy showed encouraging efficacy and tolerable safety profile. This exploratory study aims to investigate putative biomarker(s) predicting therapeutic response and long-term outcome for eligible patients. Methods: Advanced NSCLC pts who had failed standard platinum doublet without receiving any ICIs before would receive docetaxel (75mg/m2, day 1) plus sintilimab (200mg, day 3) every 3 weeks for 4-6 cycles followed by sintilimab maintenance until disease progression, unacceptable toxicity, or up to 2 years. Thirty-nine eligible patients received comprehensive genomic profiling of circulating tumor DNA (ctDNA) via a 448-gene panel before treatment. ctDNA from twenty-three patients were dynamically assessed after two courses (at 6th week). Eventually, 22 patients were enrolled into analysis, one patient was lost. White blood cells were used to filter germline variants from ctDNA sequencing data. Results: Of 22 patients with paired ctDNA profiling results at 6th week, 11 patients (50%) were defined as ctDNA residual due to presence of ≥2 somatic variants; Another 11 patients (50%) who had ≤1 somatic variant were defined as non-ctDNA residual. Significant difference of best objective response rate (ORR) (63.64% vs 0%, P=0.0039, two-sided Fisher’s Exact Testing for non-ctDNA residual vs ctDNA residual patients) was observed between these two populations. And numerically higher disease control rate (DCR) was seen in non-ctDNA residual patients (100% vs 63.64%, non-ctDNA residual vs ctDNA residual). Further, patients with ctDNA residual after 2 courses of sintilimab plus docetaxel (at 6th week) displayed higher risk of disease progression [Hazard Ratio (95%CI), 9.91(2.09-46.97), P=0.0038] and inferior prognosis (median PFS, ctDNA residual vs non-ctDNA residual, 3.0 months vs NR, P=0.0007). In addition, mutations of EGFR and LRP1B were enriched in ctDNA residual group. Especially, LRP1B gene mutations associated with shorter PFS period, which should be further investigated. Conclusions: Residual of ctDNA at 6th week was able to indicate inferior response to sintilimab plus docetaxel in patients with previously treated advanced NSCLC. Further validation of ctDNA residual as a robust predictive biomarker is warranted. [Table: see text]
Adverse events and estimated costs with the combination of ipilimumab and nivolumab in metastatic melanoma patients.
Authors: Moura Bianca Gautron , Gérard Camille Léa , Testart Nathalie , Caikovsky Marian , Wicky Alexandre M. , Aedo-Lopez Veronica , Berthod Grégoire , Homicsko Krisztian , Prior John , Dromain Clarisse , Kandalaft Lana E. , Cuendet Michel A. , Michielin Olivier 
Published: June 2021

e21529 Background: The combination of ipilimumab and nivolumab in metastatic melanoma patients increases response rates (RR) and survival outcomes. As checkpoint inhibitors bear a significant financial impact on the healthcare system, we performed a study that addresses the global costs of the treatment, focusing on immune-related adverse event (irAE) management costs. Methods: We conducted a retrospective analysis of 62 metastatic melanoma patients treated with ipilimumab and nivolumab at the Oncology Department of Lausanne University Hospital (CHUV) between June 1, 2016 and August 31, 2019. The frequency of irAEs, the duration, management, and outcomes were evaluated. All melanoma-specific costs were analyzed by mining the electronic healthcare record and billing data of the hospital. Results: The median follow-up was 32 months (range 20-1066 days). In our cohort, 54/62 (87%) patients presented at least one irAE, and 22/62 (35%) presented a grade 3 irAE. One patient died from an irAE (pneumonitis). The most common irAEs were diarrhea 23/62 (37%) any grade, 8/62 (13%) grade 3-4; hepatitis 22/62 (36%) any grade, 9/62 (15%) grade 3-4; and skin rash 21/62 (34%) any grade, 6/32 (10%) grade 3-4. The overall response rate was 29/62 (47%), with 15/62 (24%) of complete response (CR) and 14/62 (23%) of partial response (PR). The majority of patients who had a CR 13/15 (87%) and 20/28 (71%) of overall responders presented a grade 3-4 toxicity, and there were no responses in patients without toxicity. However, toxicity does not imply response, as only 29/54 (54%) of patients with toxicity (any grade) and 20/31 (65%) (grade 3-4) responded. The toxicity costs represent only 3% on average of the total expenses per patient. The most significant contributions were medication costs (44%) and disease costs (39%, mainly disease-related hospitalization costs). Patients with a CR had the lowest global cost per week (2,860 USD, converted from CHF) despite the associated toxicities and patients who had progressive disease, the highest one (9,999 USD). Except for the one patient who had a grade 5 toxicity (7,472 USD/week), we observe that less severe toxicity grades (11,603 USD/week for grade 1), or even the absence of toxicity (12,266 USD/week), are associated to higher median costs per week (against 4,039 USD/ week for grade 4 and 3,524 USD/week for grade 3). Conclusions: The cost of toxicities was unexpectedly small (only 3%) compared to the total costs, especially medication costs (44%). Also, patients with a higher degree of toxicity had lower costs and better outcomes.
Contextualizing a single-arm trial of ceralasertib (cer) plus paclitaxel with real-world data (RWD) in patients (pts) with advanced melanoma previously treated with anti-PD-(L)1(PDx) therapies.
Authors: Jiang Miao , Lee Jeeyun , Jackson Daniel , Smith Simon , Khosla Sajan , LoembE Bienvenu , Dean Emma , Smith Claire 
Published: June 2021

e21542 Background: Metastatic melanoma, especially in pts who do not respond to PDx therapy, is an area of high unmet need. Chemotherapy may be used but clinical efficacy is limited. A recent Phase I study (NCT02630199) showed that cer + paclitaxel had promising anti-tumor activity with durable responses in 34 melanoma pts after failing PDx therapy. Given the lack of published prospective clinical trial data in the post-PDx setting, RWD was used to contextualize the results of the trial. Methods: Adult pts (≥18 years) diagnosed with advanced melanoma between Jan2011-Jun2020, who received PDx therapy alone or in combination with anti-CTLA4, and also received chemotherapy immediately after the PDx line (chemo cohort) were selected from the nationwide US-based Flatiron Health EHR-derived de-identified database. A subgroup of pts who received taxane was also selected. Overall survival (OS) was assessed using Kaplan-Meier methods. Key covariates such as age, gender, LDH level, number of prior lines of therapy, presence of brain and liver metastases, and prior BRAF/MEK treatment, were adjusted using propensity score-based weighting approach. Cox regression models were used to obtain the effect estimates for OS comparing the trial arm against the RWD cohorts. Results: A cohort of 114 pts met the inclusion criteria, of which 69 received taxane. Compared with the trial arm, the RWD cohorts were older, contained more males, with higher proportions receiving prior BRAF/MEK inhibitors, with brain metastasis, and LDH≤ULN. Median OS was 7.4 months (mo) in the trial arm, compared to 5.6 (unadjusted) and 3.5 mo (adjusted) in the chemo cohort. Hazard ratio of 0.49 (95% CI: 0.29-0.83, trial vs. chemo) indicated significant benefits of the trial arm over the chemo cohort. Analyses using taxane subgroup showed similar findings. Conclusions: The RWD cohorts demonstrated poor outcomes for the pts receiving chemotherapy, in particular taxanes, confirming this is a population of unmet need. The results show the potential for improved outcomes using cer + paclitaxel in pts previously treated with PDx.[Table: see text]
Talimogene laherparepvec with systemic immunotherapy in melanoma: A real-world experience.
Authors: Behera Tapas Ranjan , Chen Yanwen , Song Jung Min , Huang Steve Shih-lin , Funchain Pauline , Gastman Brian 
Published: June 2021

e21549 Background: Talimogene laherparepvec (TVEC) is an FDA approved oncolytic herpes virus for intralesional therapy in unresectable metastatic melanoma. Real world data is sparse regarding the efficacy of TVEC in combination with other systemic therapies used in melanoma. We present outcomes of the largest single institution observational study of the off-label use of TVEC in combination with systemic immunotherapy. Methods: Patients with metastatic melanoma receiving TVEC simultaneously with ipilimumab-nivolumab (Ipi/Nivo) or single agent immunotherapy (either nivolumab or pembrolizumab) were evaluated. The demographics, clinicopathological characteristics, responses to injected lesions and remote metastatic lesions were evaluated. Clinical documentation was used to assess improvement in injected lesion size; time points for initial response and best response were identified. Review of imaging by a radiologist was evaluated to assess responses in remote metastatic lesions. Results: A total of 67 patients receiving TVEC from 2016 to 2020 were evaluated, of which 50 remained evaluable after excluding Merkel cell carcinoma, patients on clinical trial, TVEC monotherapy or those on BRAF-MEK inhibitors, and patients lost to follow up. In total, 29 received systemic immunotherapy simultaneously with TVEC and had been followed for at least a year, with a median follow-up time of 34 months (range, 12-56). At the time of analysis, 14 of 29 patients were alive. 6 of the 29 patients had received prior lines of therapy. Four patients received Ipi/Nivo, while 25 patients received monotherapy including 9 on nivolumab and 16 on pembrolizumab. The median number of TVEC doses received was 6 (range, 2-55) with median average TVEC dose being 3.47 ml (0.5-4 ml). Median time to initial local response was 6 weeks, whereas time to best local response was 14 weeks. Overall response rate in the injected target lesions was in 19 (66%), with complete local response (CR) in 12 (41%), partial response (PR) in 7 (24%), and progressive disease (PD) in 8 (28%). The response rate in distant non-injected lesions was 4 out of 16 (25%), 2 of which had previously progressed on prior systemic therapy. Stable disease was observed in 8 (50%) patients, and progression of disease in 4 (25%). The 1-year overall survival rate in patients receiving TVEC with systemic monotherapy was 80%, 95% CI 0.651-0.9730. Progression free survival at 1-year in the monotherapy group was 71.6%, 95% CI 0.557-0.918. Conclusions: This is the largest single institution, real world experience to our knowledge, which assesses the efficacy of TVEC in combination with systemic immunotherapy. Our cohort suggests that TVEC is an effective treatment in combination with systemic immunotherapy, with a better overall survival observed with combination TVEC and anti-PD1 than seen with historical data from clinical trials of anti-PD-1 monotherapy.