bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and safety profile of lurbinectedin in second-line SCLC patients: Results from a phase II single-agent trial.
Authors: Paz-Ares Luis G. , Trigo Perez Jose Manuel , Besse Benjamin , Moreno Victor , Lopez Rafael , Sala Maria Angeles , Ponce Aix Santiago , Fernandez Cristian Marcelo , Siguero Mariano , Kahatt Carmen Maria , Zeaiter Ali Hassan , Zaman Khalil , Boni Valentina , Arrondeau Jennifer , Martinez Aguillo Maite , Delord Jean-Pierre , Awada Ahmad , Kristeleit Rebecca Sophie , Olmedo Garcia Maria Eugenia , Subbiah Vivek 
Published: March 2020

8506 Background: Lurbinectedin (L) is a novel anticancer drug that inhibits activated transcription and induces DNA double-strand breaks, leading to apoptosis. Methods: A multicenter phase 2 basket trial assessed the efficacy and safety of L in several cancer types, including small cell lung cancer (SCLC). Primary endpoint was confirmed overall response rate (ORR) by RECIST v.1.1. In the SCLC cohort, a target ORR ≥30% was set. One-hundred and five patients (pts) with ECOG PS 0-2 who had received one prior chemotherapy line were treated with L 3.2 mg/m2 as a 1-hour i.v. infusion on Day 1 q3wk. Results: Median age was 60 years (range, 40-83), 60% were male, ECOG PS 0/1/2 (32%/62%/6%), liver metastasis 41%, history of CNS involvement 3.8%, prior platinum 100%, median chemotherapy-free interval (CTFI): 3.5 (0-16.1) months; prior immunotherapy (IO): 7.6%. Pts received a median of 4 cycles (range, 1-24). Conclusions: L monotherapy is active in second-line SCLC in both resistant and sensitive disease. The acceptable and manageable safety profile is also associated to a convenient treatment administration (Day 1 q3wk). L as second-line treatment in SCLC emerges as a new promising drug for this unmet clinical need. Clinical trial information: NCT02454972. [Table: see text]
Neoadjuvant chemo-immunotherapy for the treatment of stage IIIA resectable non-small-cell lung cancer (NSCLC): A phase II multicenter exploratory study—Final data of patients who underwent surgical assessment.
Authors: Provencio Mariano , Nadal Ernest , Insa Amelia , Garcia-Campelo Rosario , Casal Rubio Joaquín , Domine Manuel , Majem Margarita , Rodriguez-Abreu Delvys , Martinez Marti Alex , Cobo Manuel , Lopez-Vivanco Guillermo , del Barco Elvira , Bernabé Reyes , Vinolas Nuria , Barneto Isidoro , Viteri Santiago , Martín-Martorell Paloma , Jove Maria , Franco Fabio , Massuti Bartomeu 
Published: March 2020

8509 Background: Patients with stage IIIA (N2 or T4N0) are potentially curable but median overall survival is only around 15 months and complete pathologic response with conventional chemotherapy (CT) is no more than 9%. Methods: A Phase II, single-arm, open-label multicenter study of resectable stage IIIA N2-NSCLC adult patients with CT plus IO as a neoadjuvant treatment: three cycles of Nivolumab (NV) 360mg IV Q3W + paclitaxel 200mg/m2 + carboplatin AUC 6 IV Q3W followed by adjuvant NV treatment for 1 year. After complete neoadjuvant therapy, tumor assessment is performed prior to surgery. Surgery is performed in the 3rd or 4th week after day 21 of the third cycle of neoadjuvant treatment. The study aims to recruit 46 pts. The primary endpoint is Progression-Free Survival (PFS) at 24 months. Efficacy is explored using objective pathologic response criteria. We present final data on all patients included in this study that underwent surgical assessment. Results: At the time of submission, 46 pts had been included and 41 had undergone surgery. CT-IO was well-tolerated and surgery was not delayed in any patient. None of the pts withdrew from the study preoperatively due to progression or toxicity. 41 surgeries had been performed and all tumors were deemed resectable, with R0 resection in all cases. 34 pts (83%) achieved major pathologic response (MPR) (CI 95% 71-95%), and 24 (71%) of them had a complete pathologic response (CPR) (CI 95% 54-87%). Downstaging was seen in 90% (CI 95% 81-100%) of cases. By RECIST, 29 pts (71%) (CI 95% 56-85%) had partial response and 3 (7%) (CI 95% 0-16%) complete response. Conclusions: This is the first multicentric study to CT-IO in the neoadjuvant setting in stage IIIA. Neoadjuvant CT-IO with nivolumab in resectable IIIA NSCLC yields a high complete pathologic response rate that has never been seen previously and unsuspected by RECIST criteria. Preliminary correlative analyses in blood samples are included in a separate abstract. EudraCT Number: 2016-003732-20. Clinical trial information: NCT 03081689.
Prospective phase I multi-institutional trial of PD-1 blockade with pembrolizumab during concurrent chemoradiation for locally advanced, unresectable non-small cell lung cancer.
Authors: Jabbour Salma K. , Berman Abigail T. , Decker Roy H. , Lin Yong , Feigenberg Steven J. , Gettinger Scott N. , Aggarwal Charu , Langer Corey J. , Simone Charles B. , Bradley Jeffrey D. , Aisner Joseph , Malhotra Jyoti 
Published: March 2020

8511 Background: The PACIFIC study showed that consolidative Programmed Death Ligand 1 inhibition (PD-L1i) after chemoradiation therapy (CRT) improves PFS and OS in patients with Stage IIII NSCLC (Antonia et al. NEJM 2017, 2018). Limited data, however, exist regarding the incorporation of PD-L1i concurrently during CRT. We sought to assess the safety and toxicity of PD-1i using pembrolizumab (pembro) during definitive CRT for Stage III NSCLC. Methods: In this multi-center prospective Phase I clinical trial using a 3+3 design, we evaluated the timing and dosing of pembro combined with chemotherapy (carboplatin + paclitaxel weekly) and definitive RT (60 Gy in 2 Gy/day x 30 fractions) for unresectable, locally advanced Stage III NSCLC (AJCC 7thEd). Dose Cohorts (C) evaluated were--C1: full dose (FD) pembro (200 mg IV Q3 weeks) 2-6 weeks after CRT; C2: reduced dose (RD) pembro (100 mg IV Q3 weeks) starting Day 29 of CRT; C3: FD pembro starting Day 29 of CRT; C4: RD pembro starting on Day 1 of CRT; C5: FD pembro starting on Day 1 of CRT. For each cohort, pembro was continued Q3 weeks for up to 18 cycles (as monotherapy after CRT in either RD or FD based on initial dose assignment). Dose Limiting Toxicity (DLT) was defined as Grade ≥4 pneumonitis within 21 days of cycle 1 of pembro. Results: We enrolled 23 subjects from 8/2016-11/2018; median follow up (f/u) was 11.4 mo (range, 3.1 mo- 25.2 mo). Median age was 69 yrs (range 53-85); 52% were women. No DLTs were observed in any of the cohorts (C1 to C5). Grade ≥3 immune-related adverse events (irAE) occurred in 4 patients (18%). irAE’s included: Grade 5 (bilateral), 3, 2 pneumonitis (n=1, 1, 4, respectively (6 total)); Grade 3 hyperglycemia (n=1); Grade 3 interstitial nephritis (n=1); Grade 2 thyroiditis (n=4); Grade 2 myositis (n=1); Grade 1-2 transaminitis (n=3). Median PFS for patients who received ≥2 doses (n=18) of pembro was 20.3 mo. Conclusions: Combined treatment with PD-Li and CRT for stage III NSCLC was well tolerated with promising PFS to date but showed an increased risk for irAEs, particularly pneumonitis. Based on these encouraging results, further prospective study of PD-1i and CRT for Stage III NSCLC is warranted. Clinical trial information: NCT02621398.
Phase II trial combining atezolizumab concurrently with chemoradiation therapy in locally advanced non-small cell lung cancer.
Authors: Lin Steven H. , Lin Yan , Mok Isabel , Young Jenean A. , Phan See , Sandler Alan , Papadimitrakopoulou Vassiliki , Heymach John , Tsao Anne S. 
Published: March 2020

8512 Background: Consolidation durvalumab after chemoradiation (CRT) is the new standard of care in locally advanced NSCLC (LA-NSCLC). We hypothesized that adding immunotherapy concurrently with CRT (cCRT) would increase efficacy without significant additive toxicity. To test this concept, we conducted a phase II trial called DETERRED combining atezolizumab (atezo) with cCRT followed by consolidation full dose carboplatin/paclitaxel (CP) with atezo (CP-atezo) for 2 cycles and then maintenance atezo for 1 year. The primary endpoint was safety/toxicity and feasibility. Methods: This study enrolled patients (pts) between February 2016 - April 2018 and was done in two parts: In part 1 (N=10), conventionally fractionated CRT (60-66 Gy in 30-33 fractions combined with weekly low dose CP) was followed by CP-atezo then maintenance atezo. Part 2 was cCRT (N=30) with atezo followed by CP-atezo then maintenance atezo. Atezo was given at 1200 mg IV Q3 weeks. Severe adverse events (SAEs) ≥ grade 3 were defined by CTCAE v5.0. Evaluable pts received at least one dose of atezo. PD-L1 staining utilizes the DAKO 22C3 platform. Kaplan Meier were analyzed for progression free survival (PFS) and overall survival (OS), and chi-square test for PD-L1 levels on any recurrence, with significance set at <0.05. Results: In Part 1, atezo related SAEs were seen in 4 pts (40%) (2 grade 3 arthralgia, 1 grade 3 dyspnea and 1 grade 5 TE fistula). Grade 2 radiation pneumonitis (RP) was seen in 1 pt. In Part 2, seven (23%) pts had atezo related SAEs (diarrhea, nephritis, dyspnea, fatigue and heart failure). RP was seen in 3 pts, 2 grade 2 and 1 grade 3, which led to atezo discontinuation. In Part 1, with an overall median follow up (f/u) time of 22.5 months and 27.4 months for survivors, the 1-year PFS is 50%, and OS is 79%. In part 2, with a median f/u time of 11.8 months and 13.7 months for survivors, the 1-year PFS was 57%, and OS is 79%. Baseline tumor biopsy PD-L1 status was evaluable for 34 pts. There were no significant differences in cancer recurrence for PD-L1 <1% (7/16=44%) vs ≥1% (6/18=33%), or for the PD-L1 cutoff of <50% (11/26=42%) vs ≥50% (2/8=25%). Conclusions: Concurrent atezo with CRT followed by CP-atezo and maintenance atezo is safe without increased toxicities compared to CRT alone followed by CP-atezo and maintenance atezo. Updated efficacy results from DETERRED will be presented. Ultimately, the clinical benefit of immunotherapy with cCRT followed by consolidation chemo-immunotherapy will need to be compared to the PACIFIC regimen in a larger randomized trial. Clinical trial information: NCT02525757.
Refining the role of adjuvant chemotherapy in stage IB and IIA NSCLC.
Authors: Pathak Ranjan , Hoag Jessica R , Goldberg Sarah B. , Monsalve Andres F , Resio Benjamin , Boffa Daniel J. 
Published: March 2020

8519 Background: The role of adjuvant chemotherapy (AC) in stage IB (pT2aN0) and IIA (pT2bN0) non-small cell lung cancer (NSCLC) is currently unclear. Existing guideline recommendations are inconsistent, ranging from all tumors >4 cm, to any patient with “high-risk features” (visceral pleural invasion (VPI), lymphovascular invasion (LVI), high grade, or sublobar resection). We used the National Cancer Data Base (NCDB) to clarify the role of AC in pT2N0 patients. Methods: The NCDB was queried for treatment-naïve, post-R0 resection, pT2N0 (AJCC 8th edition) NSCLC patients between 2010 & 2014. Patients treated with single-agent AC were excluded. Survival was calculated from 30 days after surgery to minimize immortal time bias. Multivariable Cox proportional hazards regression was used to estimate the association between AC and survival across tumor sizes (T2a: 3-4 cm and T2b: 4-5 cm to reflect guideline stratifications) and risk features. Results: Of the 10,127 patients identified, 1,856 (18%) received multi-agent AC. AC patients tended to be younger (median age 64 vs 70 yrs, p<0.001), privately insured (40% vs 24%, p<0.001), treated at a non-academic center (71% vs 66%, p<0.001), and comorbidities-free (53% vs 48%, p<0.001). In T2a patients (N=6,699), AC was not significantly associated with a mortality reduction, regardless of the presence of any high-risk features. In T2b patients (N=3,428), AC (N=931, 27%) was associated with a lower mortality (HR 0.77, 95% CI 0.65-0.9, p=0.001). However, in the absence of any high-risk features (N=1414, 41% of the 4-5 cm cohort), AC was not significantly associated with survival benefit (Table). Conclusions: The presence of high-risk features does not appear to support the guideline recommendations regarding the use of AC in stage IB patients with 3-4 cm tumors. On the other hand, the benefit of AC for 4-5 cm tumors may be limited to patients with at least one high-risk feature. [Table: see text]
Three-year overall survival update from the PACIFIC trial.
Authors: Gray Jhanelle Elaine , Villegas Augusto E. , Daniel Davey B. , Vicente David , Murakami Shuji , Hui Rina , Kurata Takayasu , Chiappori Alberto , Lee Ki Hyeong , Cho Byoung Chul , Planchard David , Paz-Ares Luis G. , Faivre-Finn Corinne , Vansteenkiste Johan F. , Spigel David R. , Wadsworth Catherine , Taboada Maria , Dennis Phillip A. , Ozguroglu Mustafa , Antonia Scott Joseph 
Published: March 2020

8526 Background: In the phase 3 PACIFIC study of patients with unresectable, Stage III NSCLC without progression after chemoradiotherapy (CRT), durvalumab demonstrated significant improvements versus placebo in the primary endpoints of progression-free survival (HR, 0.52; 95% CI, 0.42–65; P < 0.0001) and overall survival (OS; HR, 0.68; 95% CI, 0.53–0.87; P = 0.00251). Safety was similar and durvalumab had no detrimental effect on patient-reported outcomes. Here, we report 3-year OS rates for all patients randomized in the PACIFIC study. Methods: Patients with WHO PS 0/1 (any tumor PD-L1 status) who received ≥2 cycles of platinum-based CRT were randomized (2:1), 1–42 days following CRT, to receive durvalumab 10 mg/kg intravenously every 2 weeks or placebo, up to 12 months, and stratified by age, sex, and smoking history. OS was analyzed using a stratified log-rank test in the ITT population. Medians and OS rates at 12, 24 and 36 months were estimated by Kaplan-Meier method. Results: In total, 713 patients were randomized of whom 709 received treatment (durvalumab, n = 473; placebo, n = 236). The last patient had completed the protocol-defined 12 months of study treatment in May 2017. As of January 31, 2019 (data cutoff), 48.2% of patients had died (44.1% and 56.5% in the durvalumab and placebo groups, respectively). The median duration of follow-up was 33.3 months (range, 0.2–51.3). Updated OS remained consistent with that previously reported (stratified HR 0.69, 95% CI, 0.55–0.86), with the median not reached (NR; 95% CI, 38.4 months–NR) with durvalumab versus 29.1 months (95% CI, 22.1–35.1) with placebo. The 12-, 24- and 36-month OS rates with durvalumab and placebo were 83.1% versus 74.6%, 66.3% versus 55.3%, and 57.0% versus 43.5%, respectively. After discontinuation, 43.3% and 57.8% in the durvalumab and placebo groups, respectively, received subsequent anticancer therapy (9.7% and 26.6% subsequently received immunotherapy). OS subgroup results will be presented. Conclusions: Updated OS data from PACIFIC, including 3-year survival rates, underscore the long-term clinical benefit with durvalumab following CRT and further establish the PACIFIC regimen as the standard of care in this population. Clinical trial information: NCT02125461.
Alteration in tumor immune microenvironment after chemo-radiotherapy for locally advanced non-small cell lung cancer.
Authors: Yoneda Kazue , Kuwata Taiji , Mori Masataka , Kanayama Masatoshi , Kuroda Koji , Ichiki Yoshinobu , Tanaka Fumihiro 
Published: March 2020

8530 Background: The consolidation treatment with durvalumab, an anti-PD-L1 antibody, after concurrent chemo-radiotherapy (CCRT) has become a new standard of care for locally advanced non-small cell lung cancer (LA-NSCLC). The rationale of the addition of anti-PD-L1 antibody is based on preclinical evidence suggesting that chemotherapy and radiotherapy may up-regulate PD-L1 expression on tumor cells. However, there has been reported no clinical evidence showing up-regulation of PD-L1 expression after CCRT. Methods: LA-NSCLC patients with paired sufficient histologic specimens for immune-histochemical analysis of tumoral PD-L1 expression (tumor proportion score, TPS) and stromal CD8-positive tumor-infiltrating lymphocyte density (CD8+density) before and after pre-operative treatment were eligible in this study. Twenty-three patients who underwent CCRT were reviewed in comparison with 18 patients who underwent chemotherapy. Results: PD-L1 expression was significantly enhanced after CCRT (median TPS, 48 from 1; P<0.01), but not after chemotherapy (median TPS, 7.5 from 1; P=0.62). No significant correlation between baseline TPS and TPS after CCRT (P=0.119). Stromal CD8+density was significantly increased after CCRT (median, 39 from 11; P<0.01) and after chemotherapy (median, 23 from 12; P<0.01). No significant correlation between baseline TPS and TPS after CCRT (P=0.378). Among CCRT cases, stromal CD8+density after treatment was significantly higher in cases with higher pathologic response to CCRT (median, 55 versus 27; P<0.01), and higher stromal CD8+density was a significant factor to predict a favorable survival after surgery (P=0.03 for recurrence-free survival; P=0.02 for overall survival). Conclusions: PD-L1 expression was significantly upregulated after CCRT regardless of baseline PD-L1 status, which may provide a pathologic rationale for the use of anti-PD-L1 agent after CCRT to improve the prognosis. Stromal CD8+density also increased after CCRT, which was correlated with pathologic response to CCRT and provided a significant prognostic impact.
10-year patient journey of stage III non-small cell lung cancer patients: A single-center, observational, retrospective study in Korea real-time automatically updated data warehouse in health care (UNIVERSE - ROOT study).
Authors: Park Keunchil , Jung Hyun Ae , Sun Jong-Mu , Lee Se-Hoon , Ahn Jin Seok , Ahn Myung-Ju , Lee Joohwan 
Published: March 2020

8536 Background: The current standard of care (SoC) for locally advanced stage III NSCLC is concurrent chemoradiotherapy (CCRT) but the outcomes are poor and unsatisfactory. The purpose of this study is to analyze the clinical features of patients with locally advanced lung cancer for 10 years in order to help develop future treatment strategy. Methods: This study through big data analysis retrospectively collected de-identified patient data from clinical data warehouse (CDW) using an unique algorithm with Standard Query Language (SQL). This new algorithm was developed by the close interactive collaboration between senior data scientists and medical oncologists. These algorithms include clinical natural language processing (NLP) systems that generate structured information from unstructured free text and structured data capture (SDC). We performed pre-processing work and data quality management (DQM) operation using over 700 clinical variables from 23,735 patients with NSCLC. Through data extraction, transformation, cleansing, and organization, we have developed a systematic and optimized program for lung cancer cohorts, including clinical features and molecular study and outcomes. It is also automatically updated every 24 hours in real time. Results: In the past 10 years, 23,735 patients were diagnosed with NSCLC and complete clinical data were available in 22,718 patients (95.7%). Out of total 22,718 patients 4,138 (18.2%) were diagnosed with stage III NSCLC. Among them, 2,676 patients (64.7%) received any type(s) of anti-cancer treatments or regular follow up at our institute. Of these 2,676 patients, 1,275 (47.6%) received curative surgery (+/- neo- and/or adjuvant CCRT); 685 (25.6%) patients definitive CCRT ; 220 (8.2%) patients palliative thoracic RT; 76 (2.8%) patients best supportive care. Median OS was 48.0 months for neoadjuvant CCRT followed by curative surgery, 51.8 months for curative surgery +/- adjuvant treatment, 29.4 months for unresected definitive CCRT (PFS 10.0 months (range: 9.1-10.9). Molecular profiles as well as updated clinical data will be presented. Conclusions: This unique in-house algorithm enables us to do a rapid and comprehensive analysis of the big data through CDW, which can be also automatically updated daily. This should provide clinically relevant information about real-world treatment outcomes and help implement or develop new treatment strategy in a timely manner.
EGFR L858R mutation as a possible target for individual-independent immunotherapy in Chinese population.
Authors: Chen Yu , Hao Shiguang , Guo Zeng-qing , Lin Jing , Chen Li-zhu , Chen Ling , Yu Jia-mi , Chen Gang , Zheng Xiong-wei , Yi Yuting , Guan Yan-Fang , Xia Xuefeng , Yi Xin 
Published: March 2020

8538 Background: Neoantigens arise from tumor-specific mutations and potentially provoke immune responses. General vaccines targeting these peptides could be beneficial for patients suffering from common cancers, like lung cancer. Therefore, a retrospective analysis was performed on 799 non-small cell lung cancer (NSCLC) tissue samples previously profiled using our 1021-gene panel. Each sample was collected from a unique patient, from whom peripheral blood or normal tissue was also obtained as control. Methods: Sequencing data were generated and pre-analyzed according to our in-house procedures. HLA typing was done using OptiType v1.0 (required sequences were captured by 1021-gene panel) and neoantigens were predicted by netMHCpan v4.0 based on typed HLA alleles and curated non-frameshift somatic mutations with frequency > 5%, which were called in pre-analysis. A neoantigen is considered mutant-specific if IC50 mut is < 500 nM and IC50 wild is > 500 nM, and especially, it is considered a strong-binder if IC50 mut is < 50 nM. Results: HLA typing returned 141 unique alleles, with the top 3 by carrier frequency being A*1101 (39%), C*0102 (33%) and A*2402 (28%). A further investigation into HLA alleles, mutations and neoantigens revealed two mutations on EGFR as candidates for off-the-shelf vaccine development: (1) L858R mutation (19%, 151 out of 799) and (2) E746_A750del mutation (13%, 106 out of 799). Among the four neoantigens derived from EGFR L858R mutation is HVKITDFGR, which can be recognized by A*3303 (IC50 mut = 22.93 nM and IC50 wild = 12,733.96 nM) and the combination is shared by 3% of the patients (23 out of 799), despite that A*3303 is not a very frequent allele in this population (16%, 127 out of 799). Two neoantigens were derived from EGFR E746_A750del mutation, including IPVAIKTSPK, which is mainly recognized by A*1101 (IC50 mut = 158.16 nM and IC50 wild = 31,132.66 nM). This combination is shared by 5% of the patients (41 out of 799). Conclusions: (1) EGFR L858R mutation and HLA-A*3303 could be a good target for individual-independent vaccine development. (2) HLA-A*1101 is the most frequent allele in this population. However, HLA-A*1101 and E746_A750del mutation is not so ideal for off-the-shelf vaccine development.