bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of pulse steroids to treat renal IRAE to maintain patients with metastatic non-small cell carcinoma cancer on pembrolizumab.
Authors: Abudayyeh Ala , Abdelrahim Maen , Fossella Frank V. 
Published: May 2020

e21589 Background: Immune checkpoint inhibitor (ICI) has a major clinical success in many cancers including non-small cell lung cancer. Renal Immune related adverse events is one of the rare IRAE’s with a reported incidence of 3-5%. In this abstract we present two cases of patients with metastatic NSCL cancer with biopsy proven acute interstitial nephritis and maintained on pembrolizumab with co-treatment of steroids. Methods: We reviewed all patients diagnosed with NSCL cancer and treated with ICI who have been diagnosed with biopsy proven AIN. We selected only the patients who were re-challenged with ICI and co-treated with steroids. Results: Two patients were identified. First patient a 40 y.o. female who was diagnosed with metastatic NSCLC. Patient was started on carboplatin, alimta, and pembrolizumab. After cycle 4 she acute kidney injury where creatinine increased to 3.26mg/dl from baseline 0.69mg/dl she was initially pulsed with steroids due to suspected renal IRAE. A kidney biopsy that indicated acute tubular necrosis which is likely related to pemetrexed and/or carboplatin. In addition, she did have acute tubular interstitial nephritis related to pembrolizumab. Creatinine stabilized at 2.0mg/dl and was continue only on pembrolizumab for the last 5 months with prednisone 40mg daily tapered off over 4 days. She has maintained her creatinine at 2.0mg/dl with continued excellent disease control. Second patient diagnosed with poorly differentiated non-small cell carcinoma with metastatic disease and PD-L1 expression is 80-90%. She was initially started on carboplatin, alimta, and pembrolizumab with complete response after 4 cycles. Her creatinine peaked to 1.84mg/dl from baseline of 0.67mg/dl. A kidney biopsy revealed chronic active interstitial nephritis. She was treated with a prednisone taper and creatinine improved to 1.1mg/dl. Patient was continued on pembrolizumab and maintained for 14 months on prednisone (as above) and sustained complete tumor response. Conclusions: Steroids in patients with persistent AIN after re-challenge may provide an excellent option to continuation of treatment. As demonstrated above, use of steroids is controversial since concern of impact on tumor response; however, smaller doses for short duration maybe efficacious in treatment of renal IRAE without impact on tumor response. Further studies need to be initiated to evaluate this intervention and its long term effects.
Efficacy and safety of DCVAC/LuCa Treatment plus standard chemotherapy and TCM in patients with advanced non-small cell lung cancer: A single-arm phase II study.
Authors: Lou Yanni , Jia Liqun , Liu Qing , Li Liya , Cui Huijuan , Deng Chao , Liu Meng , Su Fei , Cheng Zhiqiang , Wan Donggui 
Published: May 2020

e21590 Background: Lung cancer remains the leading cause of cancer-related death in China. DCVAC/LuCa is an active autologous cellular immunotherapy consisting of autologous DCs loaded with NSCLC antigens from NSCLC cell lines. SQFZ is a kind of TCM injection commonly uesed for NSCLC, made from Ginseng and Astragalus membranaceus. Intent of this study is to evaluate the efficacy and safety of DCVAC/LuCa plus chemotherapy and TCM in patients with advanced NSCLC and wild type driving gene(EGFR/ALK). Methods: This study consist of screening/leukapheresis/treatment/follow-up period. On the treatment period, chemotherapy started after leukapheresis. Four cycles are recommended with limitation to maximum 6 cycles. Up to 12 subcutaneous doses of DCVAC/LuCa treatment were administrated on the 15th day of chemotherapy cycle every 3 weeks for 4 doses, and continued alone after chemotherapy finishes/stops every 6 weeks for the remaining 8 doses. TCM therapies were administered on the -3 to 3 days of DCVAC/LuCa. After completion of the total 12 doses DCVAC/LuCa or discontinuation of study treatment, patients will be followed up until experienced OS event or till 1 year of survival time. The primary efficacy endpoint included ORR, PFS and survival. Results: 23 pts were included, 19 males and 4 females, median age 63(48-80). Pathological type:16 adenocarcinoma, 5 squamous cell carcinoma and 1 other. 7 Ⅲb and 16 Ⅳ stage. ORR was 17.39%(4/23), DCR was 60.87%(14/23). Median PFS was 10.9 months, median follow-up in surviving patients was 22.3 months, 1-year survival is currently 92.86%, 18-months survival is currently 79.59%. 1 case was diagnosed as acute myelogenous leukemia myelodysplastic syndrome after 9 doses of DCVAC/LuCa. There were no other adverse events related to DCVAC/LuCa treatment TCM therapies in this study. Conclusions: DCVAC/LuCa, combined with standard chemotherapy and TCM had exhibited the potential to improve the survival in patients with advanced NSCLC, and decrease the occurrence of adverse events. But the sample size of this study is small, a further clinical investigation is needed.
YES1 amplification as a primary driver of lung tumorigenesis and YES1/YAP1 amplifications as mediators of acquired resistance (AR) to ALK and EGFR tyrosine kinase inhibitors (TKIs).
Authors: Sato Hiroki , Kubota Daisuke , Paik Paul K. , Qiao Huan , Jungbluth Achim A , Rekhtman Natasha , Schoenfeld Adam Jacob , Yu Helena Alexandra , Riely Gregory J. , Lovly Christine Marie , Ladanyi Marc , Fan Pang-Dian 
Published: May 2020

e21591 Background: Our previous work identified YES1 amplification as a mechanism of AR to EGFR TKIs. The current study investigates the potential role of YES1 amplification as a primary driver of tumorigenesis and of YES1/YAP1 amplifications as mediators of AR to ALK and EGFR TKIs. Methods: Models of ectopic expression were established and characterized for YES1 and YAP1 in human bronchial epithelial cells (HBECs) and ALK fusion-positive ( ALK+) and EGFR-mutant ( EGFRm) lung adenocarcinoma (LUAD) cell lines. MSK-IMPACT data for all LUAD cases and for ALK and EGFR TKI AR cases were surveyed for YES1 and YAP1 amplification. Results: YES1 was found to be amplified in 0.5% of all LUAD cases currently in the MSK-IMPACT database. To demonstrate its potential as a primary driver of tumorigenesis, YES1 was inducibly expressed in HBECs and shown to promote EGF-independent growth, focus formation, and increases in proliferation rate and sensitivity to Src family kinase (SFK) TKIs. Consistent with these findings, a partial response by RECIST criteria to third-line dasatinib was observed for a patient with stage IV LUAD in which MSK-IMPACT detected YES1 amplification and no established primary driver alteration. In models of AR, overexpression of either YES1 or YAP1 in multiple ALK+ and EGFRm cell lines conferred resistance to ALK and EGFR TKIs. Sensitivity to ALK or EGFR TKIs was partially recovered in YES1-overexpressing cells lines by siRNA-mediated gene knockdown of YAP1, and was restored in YAP1-overexpressing cells lines by knockdown of YES1 or mutation of the YES1-phosphorylation site on YAP1. ALK + or EGFR m cells overexpressing either YES1 or YAP1 were sensitive to dual inhibition of the primary driver and SFKs with single-agent repotrectinib or dasatinib, respectively. In contrast, treatment of YAP1-overexpressing ALK+ H3122 cells with alectinib induced changes in morphology and gene expression consistent with epithelial-to-mesenchymal transition (EMT) and rendered the cells insensitive to repotrectinib. Similar resistance to dual inhibition was seen in other YAP1-overexpressing cell lines after treatment with only ALK or EGFR blockade. To date, one LUAD case each of EGFR and ALK TKI AR has been found through MSK-IMPACT™ to be associated with YAP1 amplification. Conclusions: SFK inhibition can potentially be exploited to therapeutically target YES1 amplification as a primary driver in tumorigenesis and YES1/YAP1 amplifications as mediators of AR to ALK and EGFR TKIs.
Monitoring through flow cytometry as a biomarker of early response to checkpoint inhibitor.
Authors: Perez Ruiz Elisabeth , Onieva Zafra Juan Luis , Garcia-Aranda Marilina , Sojo Belen , Gallardo Constanza , Laborda-Illanes Aurora , Alvarez Martina , Villatoro Rosa , Bernal Jose Antonio , Jimenez Gallego Pedro , Berciano-Guerrero Miguel-Angel , Oliver Javier , Dols Manuel Cobo , Barragán Isabel 
Published: May 2020

e21603 Background: Despite the efforts, there is still no biomarker that is able to predict the response and / or that can be used in the monitoring of patients treated with check-points inhibitors (ICI). Methods: Prospective study of a panel of blood biomarkers that help predict the response to ICI treatments. Since June 2019, a total of 60 patients with non-small cell lung cancer (NSCLC) or melanoma have been included. Prior to the start of treatment (T1 moment), after the first cycle of ICI (T2), and to progression (Tp) or 6 months after the start, blood sample has been drawn to the patients and the analysis has been carried out by flow cytometry of the percentage of lymphocytes CD8, CD3, Treg, Myeloids, NK and B lymphocytes. The one.way statistical test has been carried out that allows us to see the effect of the response on the variable at each time. Results: Of the 60 patients included, we have radiological assessment in 38. 80% are patients with NSCLC. In the evaluation at 8-10 weeks we found stable disease / partial response in 25 patients (66%), 8 progressions (21%) and 2 unknown reevaluations (13%). A significant increase in CD3, CD8, CD4, and B lymphocytes was observed in responders (p < 0.005); however, an increase in NK was observed in patients in progression (p < 0.02). No significant differences in Treg have been described and the result related to myeloid cells is pending analysis. Conclusions: Our results open a door to peripheral blood monitoring as a new tool for the management of ICI. However, our data are preliminary, having not yet reached the expected sample size and with aspects that we must clarify as the increase in NK in progressors. In addition, the final objective of this study is to generate a score combining several biomarkers of blood and tissue to be used as a predictor of response to ICI (data pending analysis).
Observation of clinical efficacy and survival of lung cancer patients with UMIPIC combined with low-dose chemotherapy.
Authors: Feng Jianbin , Jing Peng , Gao Feng , Liu Jian , Han Wei , Xu Xingyou , Zhang Xiaomin , Zhang Peicheng , Shang Wei , Teng Ye , Wu Yanfei , Yu Baofa 
Published: May 2020

e21605 Background: To observe the clinical efficacy and survival of UMIPIC combined with low-dose chemotherapy in patients with lung cancer. Methods: 840 patients with lung cancer underwent UMIPIC treatment from January 2011 to December 2015 were selected as the study subjects, 341 cases combined with low-dose chemotherapy in group A and 499 cases not combined with chemotherapy in group B. All patients were diagnosed with lung cancer and signed a consent form for treatment. The patients were treated according to the UMIPIC treatment guidelines. This study was mainly to observe the adverse reactions, clinical efficacy, survival time and survival rate of lung cancer patients after receiving UMIPIC combined with or without low dose chemotherapy. Results: The common adverse reactions in group A were fever 38.12%, followed by pain 9.38%, hemoglobin 7.94%, white blood cells 5.01%, nausea 2.35%, liver function damage 1.19%, vomiting 1.17%, and kidney function damage 0.30%; Common adverse reactions in group B were fever 38.68%, followed by pain 13.23%, hemoglobin reduction 12.87%, white blood cell reduction 5.29%, nausea 2.00%, vomiting 2.00%, liver function damage 1.92%. The hemoglobin reduction in group A was significantly lower than that in group B (P < 0.05), and there was no difference in the other adverse reactions (P > 0.05). Clinical efficacy of the two groups revealed that the benefit rate of group A was 95.45% higher than that of group B 93.47% (P > 0.05). After follow-up, it was found that the average survival time and median survival time of patients in group A were 20.744 and 13.270 months, respectively, which were significantly higher than those of group B at 19.514 and 10.070 months (P < 0.05). The survival rates of the two groups of patients, The 1-year, 2-year, and 5-year survival rates of group A patients are 52.48%, 23.60%, and 16.95%, and the 1-year, 2-year, and 5-year survival rates of group B patients are 42.96% and 17.07 % And 10.26%, the one-year survival rate of group A was significantly higher than that of group B (P < 0.05). Conclusions: UMIPIC combined with low-dose chemotherapy has a good clinical effect in treating lung cancer without increasing the incidence of adverse reactions, and a significant effect on extending survival time and improving survival rate of lung cancer patients.
Prevalence of uncommon epidermal growth factor receptor (EGFR) alterations detected in circulating tumor DNA (ctDNA) of non-small cell lung cancer (NSCLC) patients from East Asia.
Authors: AHN Beung-Chul , Loong Herbert H. F. , Chan Oscar Siu-Hong , Lee Michelle Mei Lin , Olsen Steven R. , Cho Byoung Chul , Mok Tony S. K. 
Published: May 2020

e21608 Background: EGFR is the most commonly altered biomarker in East Asian NSCLC patients. Common driver mutations (L858R or exon 19 deletions (del)) are the focus of conventional hotspot testing which may overlook less common activating alterations such as single nucleotide variants (SNVs) in the tyrosine kinase or extracellular domain as well as exon 20 insertions (ins). We investigated the prevalence of uncommon EGFR mutations in ctDNA from NSCLC patients in East Asia tested by a commercially available comprehensive next generation sequencing (NGS) assay (Guardant360). This assay identifies SNVs, ins and del, fusions, and amplifications (amp), with complete exon sequencing of EGFR. Methods: Guardant360 test results from Hong Kong, Korea, Japan, Taiwan, and Southeast Asia were reviewed (cut-off December 2019). We identified cases with a diagnosis of “lung cancer,” excluding pure squamous, small cell, neuroendocrine, carcinoid and sarcomatoid histology. Patients enrolled in certain prospective clinical trials were excluded at the investigators’ request. Clinically relevant biomarkers were mutations in EGFR, BRAF (V600E), ERBB2, or KRAS; MET amp or exon 14 skipping; and ALK, ROS1, or RET fusions. Uncommon EGFR mutations were defined as those other than L858R, exon 19 del, or resistance SNV in codons 790-797; synonymous mutations and amp were excluded. Results: Plasma from 820 non-squamous NSCLC patients was tested. Samples came from 436 women and 384 men, median age 61 years. ctDNA was identified in samples from 701 patients (85% detection rate). Alterations in at least one clinically relevant gene were detected in 75% of the ctDNA positive cases: EGFR (54%), KRAS (8%), ALK (5%), ERBB2 (5%), RET (2%), MET (2%), BRAF (1%), ROS1 ( < 1%). Uncommon EGFR alterations were found in 115 samples (16%), with 63 (9%) potentially actionable (exon 19 ins (1); exon 20 ins (22); activating SNV (40), some with multiple mutations, including L718Q (6), L718V (5), G719A (5), L861Q (5), S768I (4), and others) and 52 (7%) variants of unknown significance. Uncommon EGFR mutations were the only clinically relevant biomarker in 53 samples (8%). Conclusions: Uncommon, potentially actionable EGFR mutations were found in 9% of plasma samples from East Asian NSCLC patients. In this clinical practice dataset, uncommon EGFR mutations were more prevalent than actionable biomarkers in other genes. These data support the use of NGS testing methods to identify NSCLC patients for appropriate EGFR-targeted therapy.
Co-mutation features in treatment-naïve EGFR-mutant lung adenocarcinoma.
Authors: Zhao Jun , Fan Zaiwen , Chen Donghong , Zhuo Minglei , Liang Zhen , Li Lin , Gao Yun , Wang Xiaorong , Yu Zhuo , Cai Cunliang , Dong Dapeng , Zhao Jingquan , Gu Wenguang , Zhang Min , Chen Rongrong , Xia Xuefeng 
Published: May 2020

e21616 Background: In Chinese patients with lung adenocarcinoma, the positive rate of EGFR mutation was 40% - 50%, EGFR-TKIs therapy for lung cancer was also aimed at this part of patients. However, different EGFR mutation types have different therapeutic effects, this study focuses on different EGFR mutation types to divide the population of lung adenocarcinoma. Methods: We retrospectively reviewed gene test results of two hundred and sixty-two treatment-naïve adenocarcinoma patients. Tumor tissues (199, 76%), plasma (46, 17.5%) and other samples (17, 6.5%) were subject to next-generation sequencing using a 59-gene panel, which enables simultaneously assess SNV, Indel, rearrangements and CNV variations. Results: There were 174 females. These patients were divided into four groups, which 139 were EGFR L858R, 99 were EGFR exon 19 deletion, 7 were EGFR 20 ins and 17 were uncommon EGFR mutations, the co-mutation proportions with EGFR were 84.9% (118/139), 76.8% (76/99), 71.4% (5/7) and 94.1% (16/17) respectively. The mean numbers of co-mutation genes in L858R and exon 19 deletion were 4.173 and 3.258 (p<0.05). TP53 mutation was detected in 14.3% (1/7) 20ins group, which had a significant difference to L858R (59.7%, 83/139) and uncommon mutation groups (70.6%, 12/17) (p<0.05). Meanwhile, EGFR amplification proportion in L858R (18%, 25/139) and exon 19 deletion (6.1%, 6/99) were significantly different (p<0.05). The actionable mutations associated with target therapy involved in multiple pathways, for example, the HRR pathway and cell cycle pathway, related genes had no significant difference among the four groups. In these lung adenocarcinoma patients, we also found 6 EGFR T790M (2.3%, 6/262). Three cases accompanied with exon 19 deletion, and another three were L858R, no distribution in 20ins and uncommon groups. Conclusions: The phenomenon of concurrent gene mutation in treatment-naïve EGFR-mutant lung adenocarcinoma is common. EGFR mutant subgroups have different co-mutation features, like gene number and mutated genes. It may be the factor leading to different therapeutic effects of EGFR-TKIs, and indicate the importance of multiplex molecular test and further researches of target therapies.
Utilization patterns of immune checkpoint inhibitors (ICI) for non-small cell lung cancer (NSCLC) within the veterans health administration (VHA).
Authors: Moghanaki Drew , Jiang Renjian , Gutman David , Burns Abigail , Sukhatme Vidula , Stokes William , Ramalingam Suresh S. , Sukhatme Vikas , Behera Madhusmita 
Published: May 2020

e21630 Background: ICI are used routinely for treatment of lung cancer. We investigated the utilization of PD-1/PD-L1 inhibitors for NSCLC in the VHA. Methods: The VHA Corporate Data Warehouse was queried for data on ICI utilization in NSCLC [IRB #00113521]. The first date of any ICI dispensed was January 6, 2015 and therefore this investigation evaluated all patients diagnosed with NSCLC between 2015 –2019. Results: A total of 27,586 Veterans were diagnosed with NSCLC during the study period with demographics: 76.3% Caucasian, 16.3% black; 97.0% male; median age 71 years. Stage distribution was 27.9%, 7.9%, 15.8%, and 27.0% for stage I, II, III, or IV, respectively. A total of 3,990 patients were identified to have received any ICI, representing 20.1% of patients diagnosed with stage IV; 159 patients received more than one ICI. The median time from stage IV diagnosis to receipt of ICI was 5 months (IQR: 2-9 months). ICI was dispensed in 83.7% for duration of < 1 year, 13.3% for 1-2 years, and 3% for > = 2 years. The median duration of ICI receipt (with IQR in months): Nivolumab = 2.0 (0.5-5.5), Pembrolizumab = 2.1 (0.3-5.9), Durvalumab = 5.1 (1.8-9.2), and Atezolizumab = 0.3 (0.1-2.1). Multivariable analyses demonstrated female, not married, 0 comorbidity, and higher stage (II-IV) were independently associated with shorter time to receipt of ICI. Conclusions: The use of ICI for NSCLC is increasing within this integrated healthcare system and commonly prescribed within 5 months of stage IV diagnosis. Further investigations of this cohort using available clinical, pharmaceutical, and genomic data within the VHA present an opportunity to enhance our understanding of the efficacy of ICI for NSCLC. [Table: see text]
Efficacy of afatinib in the clinical practice: Final results of the GIDEON study in EGFR mutated non-small cell lung cancer (NSCLC) in Germany.
Authors: Brueckl Wolfgang M. , Reck Martin , Schäfer Harald , Kortsik Cornelius , Gaska Tobias , Rawluk Justyna , Krüger Stefan , Kokowski Konrad , Budweiser Stephan , Hoffmann Christopher , Schueler Andrea , Laack Eckardt 
Published: May 2020

e21636 Background: Afatinib is an irreversible ErbB family blocker, which is approved for the treatment of advanced non-small cell lung cancer (NSCLC) patients with activating EGFR mutations. Here we report the final results of the prospective non-interventional study (NIS) GIDEON, which was initiated to investigate the efficacy and tolerability of afatinib in the daily clinical routine in Germany. Methods: EGFR-mutated NSCLC patients were treated with afatinib according to label until progression, death or discontinuation. Efficacy (progression-free survival (PFS) rate at 12 months, objective response rate, ORR; disease control rate, DCR; progression-free survival, PFS and overall survival, OS) was prospectively assessed by investigators. Data about tolerability were collected during routine treatment. Results: In total, 161 patients were enrolled at 41 sites in Germany, 152 patients received at least one dose of afatinib (treated set; TS) and 146 patients were treated according to the protocol (PPS). The majority of patients for the entire TS had exon 19 deletions (64.5%), followed by L858R point mut. (22.4%) and uncommon mut. (exon 18-21 point mut.; 13.1%). The primary objective was PFS-rate at 12 months, which was 50.2% in the PPS. Median PFS amounted to 12.2 months. ORR and DCR were 74.6% and 91.5% in the PPS, respectively. Median OS was 30.4 months with 1- and 2-year survival rates of 79.1% and 57.7%, respectively. Among pat. with uncommon EGFR-mut., the 12-months PFS rate was 40.2% with a mPFS of 10.7 months. ORR and DCR were 83.3% and 91.7%, respectively. The most frequent documented adverse drug reactions (ADRs) were diarrhea and rash/acne with 13.8% and 7.2% of grade 3 but no grade 4 or higher. Conclusions: Afatinib is a standard therapy for patients with activating EGFR mut. in Germany. The final results of this prospective NIS confirm the robust clinical data for afatinib in the clinical routine setting, including patients with uncommon exon 18-21 point mutations. Clinical trial information: NCT02047903.