bluuebunny/crossref_metadata_2025_split huggingface dataset:
DNA damage response and repair (DDR) mutations predict the efficacy of platinum-based chemotherapy for advanced non-small cell lung cancer: A retrospective cohort study.
Authors: Xiao Zhiwei , Sun Lingling , Zheng Yating , Chen Hanrui , Zheng Xinting , Luo Jiamin , Gu Chuying , Xie Wenzhuan , Huang Mengli , Lin Lizhu 
Published: May 2020

e21635 Background: DNA damage response and repair (DDR) pathway alteration is known as a predictive biomarker of platinum-based chemotherapy sensitivity in urothelial carcinoma, breast cancer, ovarian cancer, and prostate cancer. However, the predictive value of DDR in patients with non-small cell lung cancer (NSCLC) is still uncertain. This study investigated the DDR mutations (MUT) of NSCLC to identify potential predictive biomarker. Methods: A retrospective analysis of patients with NSCLC was performed. Targeted exon sequencing with the Next Generation Sequencing (NGS) were performed for 298 patients, and they were divided into two groups based on the presence or absence of mutations in 36 DDR genes. Results: 50 patients treated with platinum-based chemotherapy were identified, of which 17 harbored alterations in DDR genes. The median age was 60.5 years (range, 43 to 79 years). A total of 50 patients were evaluated, the objective response rate (ORR) of patients with DDR MUT was 17.6%, ORR 0% for DDR wild-type (WT), and the disease control rate (DCR) was 76.4% for DDR MUT, 48.5% for DDR WT. In terms of survival analysis, patients with DDR MUT had significantly improved median progression-free survival (mPFS) of 9.2 months compared with 4.8 months for DDR WT (Hazard Ratio (HR) = 0.4134, log-rank P = 0.0117). When EGFR and ALK mutations were excluded, there was no significant difference in mPFS between DDR MUT and WT, but DDR MUT has a tendency to be higher than WT (mPFS: 8.0 vs. 4.7 months, HR = 0.5060, log-rank P = 0.1022). Nevertheless, there was no significant difference in the median overall survival (mOS) between two groups (DDR MUT vs. DDR WT: 21.7 vs. 29.4 months, HR = 1.537, log-rank P = 0.3756), even after EGFR and ALK mutations were excluded, no significant difference can also be gained (HR = 1.818, log-rank P = 0.3972). Conclusions: DDR mutations may be a positive predictive biomarker for response to platinum-based chemotherapy in patients with NSCLC.
Efficacy of immune checkpoint blockade alone or combined with chemotherapy and smoking status in NSCLC: A systematic review and meta-analysis.
Authors: Wang Shanshan , Lin You-En , Yang Dan , Wang Guoqiang , Cai Shangli , Qian Jun , Chen Chuan , Xiong Jianping , Xu Yu 
Published: May 2020

e21661 Background: Tobacco smoking is a critical cause of mutational burden and immuno-microenvironmental alteration in non-small cell lung cancer (NSCLC). However, the association between tobacco consumption and the synergetic effect of chemotherapy on single-agent immunotherapy remains controversial. Methods: We systematically searched PubMed, the Cochrane Central library and Embase, for the RCTs of ICI in NSCLC with HR for both PFS and OS according to smoking status. Random-effects model were used to pool estimates of survival HR and 95%CI. Subgroup analysis and meta-regression were implemented to investigate the source of heterogeneity. Results: In total, 13 eligible RCTs of 8154 NSCLC patients (6800 ever-smokers and 1354 never-smokers) were included. PFS benefit from immunotherapy comparing standard treatment remarkably differed between ever-smokers and never-smokers (P = 0.005), where significant PFS benefit was observed in ever-smokers (pooled HR = 0.72, 95%CI 0.63-0.81, P < 0.001) instead of never-smokers (pooled HR = 0.98, 95%CI 0.73-1.31, P = 0.90). In never-smokers, the choice of regimen (monotherapy vs. combination therapy) considerably impacted the benefit of PFS (HR = 2.21, 95%CI 1.35-3.61, P = 0.005) and OS (HR = 1.99, 95%CI 1.03-3.82, P = 0.041). Compared to standard treatment, monotherapy worsened PFS (HR = 1.39, 95%CI 1.01-1.90, P = 0.046) and did not improve OS (HR = 0.91, 95%CI 0.72-1.14) in never-smokers, while combination therapy dramatically delayed both progression (HR = 0.63, 95%CI 0.49-0.81, P < 0.001) and death (HR = 0.45, 95%CI 0.25-0.82, P = 0.010). Conclusions: Tobacco smoke was associated with larger PFS, but not OS benefit from immunotherapy. In never-smokers, not ever-smokers, combination with chemotherapy compared to single-agent ICI might confer significantly greater delays of both progression and death. [Table: see text]
High incidence of brain metastasis in young patients with lung adenocarcinoma.
Authors: Ramirez Ilene , Brandon Maximiliano , Abal Mariana , Martin Reinas Gaston , Marin Ordoñez Alba , Montiel Monica , Gonzalez Liliana D , Gil Deza Ernesto , Morgenfeld Eduardo L. , Rivarola Edgardo G. J. , Gercovich Felipe G. 
Published: May 2020

e21677 Background: Young patients with lung cancer are unusual. This paper focuses on our experience with Young Patients (<45 yo) with Lung Adenocarcinoma (YPLA), treated at Instituto Oncológico Henry Moore (IOHM). Methods: Out of all lung cancer patients, we selected YPLA admitted between September 2012 and September 2019. We analyzed their medical history forms, electronic clinical records, treatments and outcomes. Results: We included 31 out of 1,119 Pt (3%) patients. Median Age: 39 (24-44). Sex F/M: 15/16. The table shows the clinical characteristics of population and outcomes. Conclusions: 1) Young patients with lung adenocarcinoma presented aggressive tumors, as evidenced by: advanced stages, poor performance status and CNS compromise. 2) In our series, smoking is a predominant etiological factor. 3) Further research will analyze genomic profiles of these tumors. 4) Screening for CNS metastasis should be mandatory in this population. [Table: see text]
Progression free survival (PFS) in Asian vs non-Asian patients (pts) with EGFR mutant non-small cell lung cancer (NSCLC) receiving osimertinib.
Authors: Cytryn Samuel , Punekar Salman Rafi , Tenet Megan , Ullah Tasfiq , Wang Bin , Goldberg Judith D. , Velcheti Vamsidhar , Wong Kwok-Kin , Chachoua Abraham , Shum Elaine , Sabari Joshua K. 
Published: May 2020

e21679 Background: Third generation EGFR tyrosine kinase inhibitor (TKI) osimertinib demonstrated superior PFS and OS compared to earlier generation TKIs in pts with EGFR+ NSCLC. These pts are disproportionately Asian, female, and never-smokers. Contradictory data has been reported regarding the PFS and OS to osimertinib in Asian pts as compared to 1st and 2nd generation EGFR TKI. These inconsistencies warrant further investigation. The purpose of this study is to evaluate the PFS in Asian vs non-Asian pts with EGFR+ NSCLC receiving osimertinib. Methods: We conducted a single institution IRB approved retrospective study of pts with EGFR+ NSCLC. PFS was evaluated in pts treated from 1/2013 – 12/2019. Disease and treatment characteristics were summarized using frequency distributions and Kaplan-Meier curves for comparison of subgroups. Results: Of 190 EGFR+ pts: 52 (27%) Asian, 108 (57%) Caucasian, 125 (66%) female, 172 (91%) advanced disease, 107 (56%) never-smokers. Baseline characteristics in Asian and non-Asian pts were similar in regards to de-novo stage IV disease (71% vs 65%, p = 0.80), brain metastases (42% vs 54%, p = 0.48), and differed with regards to ever-smoking (29% vs 56%, p = 0.04). Treatment: 126/172 (73%) pts with advanced disease received TKI across all lines of therapy; 92/126 received osimertinib (22 (24%) 1st line; 45 (49%) 2nd line; 18 (19%) 3rd line; 7 (8%) ≥4th line). There were insufficient number of pts who received osimertinib in the 1st line to comment on differences in PFS between Asian and non-Asian pts. In the 2nd line, 19 Asian pts and 26 non-Asian pts received osimertinib, with no observed difference in PFS (median 15.4 v 13.8 months, p = 0.20). Moreover, Asian pts who received osimertinib as second line therapy had superior PFS (median 15.4 vs 9.6 months, p < 0.01) compared to Asian pts who received earlier generation TKIs, likely due to T790M resistance. Conclusions: Among second line advanced EGFR+ NSCLC, we did not observe a difference in PFS between Asian and non-Asian pts treated with osimertinib. Median PFS in Asian pts treated with osimertinib was longer compared to those treated with 1st or 2nd generation TKIs in the 2nd line setting. Our study highlights the the role of ethnic background in response to EGFR therapies and may warrant further study.
Interim results from the OPTIMAL trial: A phase II clinical trial of combination nivolumab, ipilimumab, and taxane in patients with untreated metastatic non-small cell lung cancer (NSCLC).
Authors: Clarke Jeffrey Melson , Wang Xiaofei F. , Gu Lin , Stevenson Marvaretta Miesha , Stinchcombe Tom , Ramalingam Sundhar , Antonia Scott Joseph , Shariff Afreen , Garst Jennifer , Crawford Jeffrey , Ready Neal E. 
Published: May 2020

e21683 Background: Combination chemo-immunotherapy is a well-established frontline therapeutic option for treatment naïve NSCLC. Dual immune checkpoint blockade (ICB) with nivolumab (nivo) and ipilimumab (ipi) has demonstrated improved clinical outcomes compared with chemotherapy alone in this setting. Combination dual ICB with low-dose chemotherapy may have advantages of preventing early disease progression and potentiating immunogenic response to treatment. Methods: We are conducting a single arm phase II clinical trial of nivo 360 mg IV Q3 weeks, ipi 1 mg/kg IV Q6 weeks, and weekly paclitaxel 80 mg/m2 IV on d1 and d8 of a 21 day cycle in ECOG 0-1 patients (pts) with treatment naïve NSCLC. Paclitaxel is stopped after a total of 4-6 cycles. The primary endpoint of the trial is progression free survival (PFS) with secondary endpoints of safety and objective response rate (ORR) by independent radiologic review. Interim results are presented from the first 23 evaluable pts, of a planned sample size of 49. Results: 23 pts were enrolled and evaluable with a mean age 63.8 years, 56.5% ECOG 0, 87% current/previous smoking history, and 70% adenocarcinoma. PDL1 score for < 1%, 1-49%, ³ 50% was seen in 9 (39.1%), 4 (17.4%), and 10 (43.5%) pts, respectively. Median time of follow up was 6.5 months (range 1.4–15.0). Partial response was observed in 14 pts, stable disease was seen in 8 pts, and 1 pt progressed during cycle 1, resulting in an ORR of 61%. Grade 3 or higher toxicity at least possibly attributed to study treatment was seen in 47.8% of 23 AE evaluable patients, of which included 4 cases of secondary adrenal insufficiency. Other toxicity rates were as expected for the respective agents. Conclusions: This is the first trial to evaluate weekly paclitaxel with nivo plus ipi in pts with untreated NSCLC. This regimen has demonstrated highly encouraging clinical activity with a manageable toxicity profile. The study is ongoing and updated results will be presented at the annual meeting. Clinical trial information: NCT03573947.
SAF-189s in previously treated patients with advanced ALK-rearranged non-small cell lung cancer (NSCLC): Results from the dose-finding portion in a single-arm, first-in-human phase I/II study.
Authors: Yang Jin-Ji , Zhou Jianying , Yang Nong , Wu Zhuli , Sun Juan , Hui Ai-Min , Wu Yi-Long 
Published: May 2020

e21689 Background: Patients(pts) with ALK-rearranged non-small cell lung cancer (NSCLC) are sensitive but progress in 8–11 months with treatment of ALK inhibitor crizotinib, with leading progression in brain metastasis. SAF-189s is a novel and selective ALK inhibitor, can penetrate through blood brain barrier, and overcome multiple resistance mutation. This study aimed to explore the safety, efficacy, and pharmacokinetic properties of SAF-189s in patients with advanced ALK-rearranged NSCLC. Methods: In this multicenter I/II study, SAF-189s was orally administered under fasting condition at doses ranging from 20–210 mg once daily in a 21-day cycle to 36 pts with advanced ALK-positive NSCLC who had failed to prior systemic therapy. In this analysis report, anti-tumor activity of SAF-189s was evaluated in 34 pts received 40(n = 6), 80(n = 8), 120(n = 8), 160(n = 9) and 210(n = 3) mg doses daily. Safety was evaluated in all 36 pts who received ≥1 treatment. This study is registered with clinicaltrials.gov, NCT04237805. Results: 36 pts were enrolled in total, 22 pts had CNS metastases at baseline and 26 pts had progressed to prior TKIs therapy. There was no treatment-related SAE among the 36 pts. The most common drug-related events were nausea (14 [38.9%] of 36 pts), vomiting (10[27.8%] of 36 pts), QT prolongation (9 [25.0%] of 36 pts), sinus bradycardia (7 [19.4%] of 36 pts), ALT increase (10 [27.8%] of 36 pts), diarrhea (6 [16.7%] of 36 pts). Only one DLT of grade 3 blood glucose increase occurred at 210 mg out of the first 3 pts, so another 3 pts will be enrolled to determine RP2D/MTD. SAF-189s had shown response in the starting dose of 20mg, with 1of 2 pts achieving partial response (PR) over 43 cycles until clinical data cut off. All 34 pts in efficacy analysis set had achieved tumor shrinkage, with 17 confirmed PR (50%) (95% CI, 32.4–67.6%) and 4 unconfirmed PR (11.7%). 11 (45.8%) pts had confirmed PR among 24 pts who had failed to Crizotinib or Ceritinib and 10 (47.6%) pts had confirmed PR among 21pts who had CNS metastases. PFS data is pre-mature, with only median PFS of the 80 mg cohort being inferred as 19.42 months. Conclusions: In the dose-escalation portion of this study, SAF-189s was safe, very tolerable, and demonstrated both systemic and intracranial activity in pts with advanced ALK-positive NSCLC who had failed to at least 1 prior systemic therapy. Therefore, this study warrants further investigation to prove SAF-189s as an effective therapeutic option for pts who have ALK+ NSCLC. Clinical trial information: NCT04237805.
Culture of circulating tumour cells derived from non-small cell lung cancer.
Authors: O'Byrne Kenneth John , Kapeleris Joanna , Kulasinghe Arutha , Warkiani Majid E , O'Leary Connor Gerard , Ladwa Rahul , Vela Ian , Leo Paul , Sternes Peter , Punyadeera Chamindie 
Published: May 2020

e21692 Background: Tumour tissue-based information is limited. Liquid biopsy can provide valuable real-time information through circulating tumour cells (CTCs). Profiling and expanding CTCs may provide avenues to study transient metastatic disease. Methods: 70 NSCLC patients were recruited. CTCs were enriched using the spiral microfluidic chip and a RosetteSep™ using bloods from NSCLC patients. CTC cultures were carried out using the Clevers media under hypoxic conditions. CTCs were characterized using immunofluorescence and mutation-specific antibodies for samples with known mutation profiles. Exome sequencing was used to characterized CTC cultures. Results: CTCs ( > 2 cells) were detected in 38/70 (54.3%) of patients ranging from 0-385 CTCs per 7.5ml blood. In 4/5 patients where primary tumours harboured an EGFR exon 19 deletion, this EGFR mutation was also captured in CTCs. ALK translocation was confirmed on CTCs from a patient harbouring an ALK-rearrangement in the primary tumour. Short term CTC cultures were successfully generated in 9/70 NSCLC patients. Whole exome sequencing confirmed the presence of somatic mutations in the CTC cultures with mutational signatures consistent with NSCLC. Conclusions: This study demonstrates a workflow for ex vivo culture of CTCs from NSCLC blood samples.
Immunotherapy efficacy of programmed cell death 1 (PD-1) versus programmed death ligand-1 (PD-L1) inhibitors in non-small cell lung cancer (NSCLC) patients: A systematic review and meta-analysis.
Authors: Yang Danrong , Cui Longgang , Zhang Yuzi , Zhao Zhengyi , Bai Yuezong 
Published: May 2020

e21700 Background: Immune checkpoint inhibitors of programmed cell death-1 (PD-1) and its ligand (PD-L1) have been new standard of care for non-small cell cancer patients. However, little is known about the difference in efficacy between these two types of drugs. In this study, we aimed to assess the differences between anti-PD-1 and anti-PD-L1 in NSCLC treatment through a systematic review and meta-analysis. Methods: We systematically searched PubMed, CENTRAL, and Embase from January, 2000 to November, 2019. We also reviewed abstracts and presentations from all major conference proceedings. All randomized controlled trials that compared anti-PD-1/anti-PD-L1 with standard treatment in NSCLC cancer patients were selected as candidates. Studies with anti-PD-1 and anti-PD-L1 were screened and paired upon the mirror principle. The primary outcome was the difference in overall survival (OS). As the main results, indirect comparison of anti-PD-1 and anti-PD-L1 were calculated for each mirror group and then pooled using a random-effects model. Results: 16 randomized controlled trials were included for the meta-analysis. Overall, anti-PD-1 exhibited superior OS (HR 0.80, 95% CI 0.68-0.95, P= .01) over anti-PD-L1. Subgroup analysis showed that anti-PD-1 exhibited superior OS over anti-PD-L1 ICIs in combination therapy (HR 0.67, 95% CI 0.54-0.82, P <.01), but not in monotherapy (HR 0.89, 95% CI 0.74-1.06), 2nd line therapy (HR 0.84, 95% CI 0.66-1.06) or 1st line therapy (HR 0.77, 95% CI 0.58-1.03). Conclusions: The results demonstrated that anti-PD-1 exhibited favorable survival outcomes compared to anti-PD-L1 in NSCLC treatment, which provides an important guide for clinicians.
Osimertinib for patients with poor performance status and EGFR T790M mutation-positive advanced non-small-cell lung cancer (NSCLC): A phase II clinical trial.
Authors: Ozawa Yuichi , Nakashima Kazuhisa , Daga Haruko , Imai Hisao , Tamiya Motohiro , Tokito Takaaki , Kawamura Takahisa , Akamatsu Hiroaki , Tsuboguchi Yuko , Takahashi Toshiaki , Yamamoto Nobuyuki , Mori Keita , Murakami Haruyasu 
Published: May 2020

e21704 Background: Osimertinib has been shown to be effective against epidermal growth factor receptor ( EGFR) T790M-positive non-small cell lung cancer (NSCLC), but so far all clinical trials have targeted performance status (PS) 0 to 1 cases. The efficacy and safety of osimertinib in EGFR T790M-positive NSCLC patients with poor PS remain elusive. Methods: We conducted an open-label, multi-center, single-arm phase II study to evaluate the efficacy and safety of osimertinib in patients with EGFR T790M mutation-positive NSCLC who had Eastern Cooperative Oncology Group PS scores of 2 to 4. Patients received 80 mg of osimertinib once daily. The primary endpoint was progression-free survival (PFS). The planned sample size was 18 patients to achieve power of at least 80% with one-sided alpha of 0.05 and expected and threshold PFS as 8.2 months and 3.0 months. Results: Eighteen patients (4 men and 14 women) were enrolled between June 2017 and November 2018. The median age was 77 years (range: 55–85 years). Ten, six, and two patients had PS scores of 2, 3, and 4, respectively. All patients had adenocarcinoma with common EGFR mutations and were previously treated with first- or second-generation EGFR- tyrosine kinase inhibitors, and 10 patients (56%) had central nervous system (CNS) metastasis. The overall median PFS was 7.0 months (90% confidence interval: 5.5-8.9 months). The overall response rate (ORR) was 53%, the median time to first response was 1.5 months, the median duration of response was 6.7 months, and the median overall survival (OS) was 12.7 months. Moreover, improved PS scores were observed in 13 patients (72%) including six with PS 2, six with PS 3, and one with PS 4. Osimertinib also showed an ORR of 60% in the patients with CNS metastasis, and the median PFS and OS were 6.5 months and 22.0 months, respectively. Although anemia, rash, and anorexia were frequently reported, the incidence of grade 3 adverse events was low, and no grade 4 or 5 events were observed. Interstitial lung disease (ILD) was observed in three patients (two with grade 2, one with grade 1). All three patients discontinued osimertinib treatment and recovered from ILD. Conclusions: Osimertinib therapy could be a promising treatment option for patients with EGFR T790M mutation-positive advanced NSCLC who have poor PS. Clinical trial information: UMIN000027655.
The impact of comorbidities and adverse events on quality of life in patients with EGFR-mutated non-small-cell lung cancer (NSCLC) receiving epidermal growth factor receptor tyrosine kinase inhibitors therapy: A multicenter prospective study.
Authors: Chen Jung Yueh , Chen Kuan-Yu , Wei Yu-Feng , Liang Sheng-Kai , Chuang Tsu-Yi 
Published: May 2020

e21708 Background: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are the standard first-line treatment for patients with advanced EGFR-mutated non-small cell lung cancer (NSCLC). However, the impact of comorbidities and treatment-related adverse events (AE) on quality of life (QOL) in patients receiving EGFR-TKI therapy was seldom investigated in a prospective setting. Methods: We conducted a prospective observational study to evaluate the association of comorbidity, AEs, and QOL in patients with EGFR-mutated advanced NSCLC receiving EGFR-TKI as first-line therapy among four hospitals in Taiwan. The questionnaires for QOL and AEs were obtained at baseline, the 2nd, 4th, 12th, and 24th week. Comorbidities were evaluated at baseline by using Simplified Comorbidity Score (SCS). The QOL was assessed by using EORTC QLQ-C30, QLQ-LC-13, and dermatology life quality index (DLQI). Paronychia related to oncologic treatments (SPOT) scale was used for paronychia severity evaluation. Visual analogue score (VAS) was applied for pain and itching evaluation. AE was recorded by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The correlations between QOL and comorbidities as well as AEs were analyzed by generalized estimating equation. Results: A total of 110 patients were included. Comorbidities were not associated with QOL deterioration (p= 0.209). While assessed by QLQ-LC13, mucositis (p= 0.001), elevated aminotransferase levels (p= 0.046), and use of oral antibiotic for dermatitis (p= 0.009) were associated with QOL deterioration. There was no significant difference in QOL among patients receiving afatinib, erlotinib, or gefitinib therapy. Gefitinib and afatinib showed a trend of improved QOL assessed by QLQ-C30 and LC13, whereas erlotinib with a trend of deteriorated QOL by LC13 (effect size = 0.07). For dermatological toxicities, a trend of deterioration in QOL was observed by DLQI assessment in patients received erlotinib (effect size = 7.44) or afatinib (effect size = 0.71). SPOT scale was higher in patients taking afatinib (p= 0.002). VAS pain score was higher in those taking afatinib (p= 0.005) or erlotinib (p= 0.049). Conclusions: Comorbidities and the choice of EGFR-TKI have no impact on overall QOL in advanced NSCLC patients receiving EGFR-TKI therapy. Mucositis, impaired liver function, and dermatitis needed oral antibiotics use may lead to a QOL deterioration.