bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunotherapy in patients with advanced stage non-squamous (non-Sq) non-small cell lung cancer (NSCLC) with activating genetic mutations: Single institution retrospective study.
Authors: Khaddour Leila , Singh Sunny R K , Rybkin Igor I. 
Published: May 2020

e21577 Background: Immunotherapy has dramatically changed the landscape of lung cancer management. However, its efficacy remains controversial in patients with activating mutations. We report retrospective analysis of clinical outcomes of advanced stage NSCLC patients with activating mutations treated with immune checkpoint inhibitors throughout their disease course. Methods: We analyze all adult patients diagnosed with advanced NSCLC in our institution between January 2014 and January 2018, and who had activating mutations in EGFR, MET, or BRAF genes or ALK rearrangement. Patients in both arms must be treated with at least one line of tyrosine kinase inhibitors (TKI). The investigation arm were patients who received immunotherapy at any time during their disease course. The control arm were patients who did not receive immunotherapy. The primary endpoint was overall survival (OS). Secondary endpoints were objective response rate (ORR) and disease control rate (DCR) in the investigation arm. Results: A total of 47 patients met the inclusion criteria: 27 patients received immunotherapy after or before TKI failure, while 20 patients did not receive immunotherapy. Baseline characteristics were similar in both groups. The average age at diagnosis was 65 years and 40% were males. 68% of patients were at stage IV at the time of diagnosis, 43% were never smokers, and 40% had brain metastases. EGFR mutations accounted for 76.6% of alterations, while ALK rearrangement was demonstrated in 17%, MET and BRAF mutations in 4.3% and 2.1% respectively. Among 27 patients in the immunotherapy group, 3 received chemotherapy simultaneously, 11 patients had received prior chemotherapy, while 13 patients were chemotherapy naive. Complete response was achieved in one case. The ORR was 22.2% and DCR was 37%. Targeted therapy was re-introduced in 9 patients after discontinuation of immunotherapy, of whom 3 responded. The median OS was 44 months (95%CI 28.9-59.4) in immunotherapy group versus 35.7 months (95% CI 23.9-47.4) in control group (P-value 0.34). Conclusions: Immunotherapy, as single agent or in combination with chemotherapy, is associated with better OS trend in patients with advanced NSCLC who harbor activation mutations and failed TKI. This effect was not statistically significant. The prospective data in this population is also limited and controversial. More trials are warranted to evaluate the efficacy of immunotherapy in this group.
Improvement in lung cancer survival: Six-year survival analysis of patients diagnosed between 2011 and 2016 in Hungary.
Authors: Bogos Krisztina , Kiss Zoltan , Tamási Lilla , Ostoros Gyula , Dr Szabone Dr Muller Veronika Judit , Bittner Nora , Sarosi Veronika , Vastag Aladar , NAGY-ERDEI ZSOFIA MARIA , Polanyi Zoltan , Daniel Andrea , Nagy Balazs , Horvath Krisztian , Abonyi-Toth Zsolt , Rokszin Gyorgy , Voko Zoltan , Moldvay Judit 
Published: May 2020

e21582 Background: Lung cancer is one of the most common cancers worldwide, however, 5-year survival is poor, only 10-20% of pataients survive this period. To date, no long-term study has been conducted to evaluate long-term survival rates in Hungary. Therefore, the objective of our study was to assess the 6-year survival of lung cancer patients (ICD-10 C34) based on a nationwide review of the National Health Insurance Fund (NHIF) database. Methods: Our retrospective, longitudinal study included patients aged ≥20 years who were diagnosed with lung cancer (ICD-10 C34) between 1 January 2011 and 31 December 2016. Screening period was set for 2009-2010. Patients with other cancer-related ICD-10 codes 6 months before or 12 months after lung cancer diagnosis and those who received any anticancer treatment different from lung cancer protocols were excluded. Survival rates were evaluated according to year of diagnosis, patient gender and age, and morphology of lung cancer and main treatment type. Results: 41,854 newly diagnosed lung cancer patients were recorded. Mean age at diagnosis varied between 64.66 and 65.88 years during study period. One- and 5-year crude survival rates for the total population were 42.23% and 17.85%, respectively. Survival was significantly associated with gender, age and type of lung cancer based on statistical association. Female patients (n = 16,362) had 23% better survival (HR: 0.77 CI95% 0.75-0.79; p < 0.001) than males (n = 25,492). The highest survival rates were found in the 20–49 age cohort (5Y = 31.3%) and if the cancer type was adenocarcinoma (5Y = 20.48%). We measured 5.3 % improvement in lung cancer survival between cases diagnosed in 2015-2016 vs. 2011-2012 (HR: 0.947 CI95% 0.92-0.97; p = 0.003). Survival of those lung cancer patients, whom had surgery in first line treatment without adjuvant therapy (3,120) reached 64.18%, those with adjuvant treatment (n = 2,675) 54.47% 5 year survival, while patients with chemotherapy (n = 11,780) had only 7.9% crude survival. Conclusions: Our study provided long-term LC survival data in Hungary for the first time. We found a 6% improvement in survival by the end of the study period in females and in the younger age groups. Survival rates were comparable to – and at the higher end of – rates registered in other East-Central European countries. Better survival rate of females could be attributed to a higher incidence rate of adenocarcinoma in women. Lung cancer patients diagnosed in early stage had 7-8 times better survival than those found in late stage.
Efficacy and safety of SHR-1210 combined with apatinib in first-line treatment for advanced lung squamous cell carcinoma: A phase II study.
Authors: Wang Jinliang , Zhang Zhibo , Yan Xiang , Ma Junxun , Zhang Fan , Song Qi , Zhang Li , Liu Zhefeng , Yang Bo , Wang Lijie , Tao Haitao , Zhang Sujie , Li Xiaoyan , Hu Jie , Li Xiaoting , Wang Jiaqian , Zhi Xiaoyu , Ge Xiangwei , Jiao Shunchang , Hu Yi 
Published: May 2020

e21587 Background: PD-1 inhibitors plus chemotherapy is a standard of first-line therapy in advanced lung squamous cell carcinoma (LUSC). Previous preclinical and clinical studies suggested that the combination of anti-PD-1 antibody SHR-1210 and VEGFR-2 inhibitor apatinib significantly improved anti-tumor effects. The aim of this study was to evaluate the efficacy and safety of SHR-1210 in combination with apatinib for advanced LUSC patients as a first-line treatment. Methods: In this phase II study, patients diagnosed with stage IIIB or IV advanced LUSC were enrolled. All patients received SHR-1210 (200mg q2w) and apatinib (250mg po qd) until disease progression or unacceptable toxicity. Treatment efficacy was assessed every 3 cycles (6 weeks). The primary endpoint is progression-free survival (PFS). Secondary endpoints are objective response rate (ORR), disease control rate (DCR), and overall survival (OS), which according to RECIST 1.1. Results: At the primary analysis (data cutoff Feb 10, 2020), 26 advanced LUSC patients had enrolled, and 17 patients of which were evaluable. Baseline characteristics were shown that median age was 67 years, male percentage was 92.3% (24/26), and clinical stage IV percentage was for 57.7% (15/26). The median follow-up time was 3.1 months (range 0.4-13.7 months) in all included patients. No complete response (CR) was reported. Partial response (PR) was achieved in 13 (76.5%) and stable disease (SD) in 4 (23.5%). The ORR and DCR in 17 evaluable patients were 76.5% and 100%, respectively. The most common treatment-related adverse events were hypertension (42.3%), rash (38.5%), hand-foot skin reaction (26.9%), and reactive cutaneous capillary endothelial proliferation (RCCEP) (15.4%). Of 26 patients, 5 experienced a grade ≥3 treatment-related adverse events, including one interstitial pneumonia, one hypertension, one thrombocytopenia, one RCCEP, and one aminotransferase elevation. Three patients (3/26) were reported dead, of which one died due to interstitial pneumonia and the others died of tumor progression. Twelve patients (46.2%) ever suspended treatment or adjusted the dosage of apatinib due to interstitial pneumonia, pyelonephritis, rash, thrombocytopenia, or aminotransferase elevation. Conclusions: The combination of SHR-1210 and apatinib for advanced LUSC patients was well tolerated and effective. This treatment may be a promising method for advanced LUSC as a first-line treatment. Fund Project (No: 2017FC-CXYY-3007) & Project (No: 2017MBD-013). Clinical trial information: ChiCTR1800019329.
BRAF fusion in lung cancer.
Authors: Zhao Jun , Guo Renhua , Ai Xinghao , Liu Lianke , Li Lin , Chen Mingjiu , Pu Xingxiang , Zhang Min , Chen Rongrong , Xia Xuefeng 
Published: May 2020

e21598 Background: BRAF was a part of RAS/MAPK pathway, which regulated the proliferation, differentiation, migration, and apoptosis of cells. BRAF V600E was a potential treatment target for non-small cell lung cancer and other tumors. While BRAF fusion was rare in lung cancer. Here we focus on BRAF fusion in lung cancer. Methods: We retrospectively reviewed next-generation sequencing (NGS) results of lung cancers, with or without treatment history. The samples were subjected to NGS using 59 or 1021-gene panel, which enables simultaneously assess snv, indel, rearrangements and cnv variations. Patients with BRAF fusion were collected and used to analysis. Results: We found eighteen lung cancers have BRAF fusion from about twelve thousand patients, 13 are females. The median age at diagnosis was 47-year old (range 28 to 70). Tested samples included 13 tissues, 5 plasma, and 2 pleural effusion. BRAF fusion could occur in different stage, 12 stage Ⅳ and 1 stage Ⅰ, other were unknown. There were 14 lung adenocarcinoma, 1 squamous cell carcinoma and 1 adenosquamous carcinoma, other two patients were unknown. The partner genes of BRAF fusion were distinctly among the patient, TRIM24 was relatively common. The median tumor mutation burden (TMB) was 4.8muts/Mb (range 0 to 15.4), with low TMB-H frequency (10.5%, defined 9 as cutoff value). Seven patients had no system treatment history, and 1 had concurrent EGFR L858R mutation. Nine patients received EGFR-TKI therapy, 1 received ALK-TKI therapy, and 1 received chemotherapy. Among the EGFR-TKI treated patients, 7 received first and third generation TKI sequential therapy, the median TTD (time to discontinue) of TKIs was 26 months (range 17 to 46). The EGFR mutation still exist when EGFR-TKIs resistance, included EGFR primary mutation, T790M, and C797S, concurrent with BRAF fusion. Except for BRAF fusion, there also had other complex resistance mechanism occurred, like HER2 mutation, KRAS mutation, etc. Conclusions: BRAF fusion had low frequency in lung cancer and occurred at different stage during disease development. BRAF inhibitors maybe a potential strategy for BRAF fusion lung cancers. As TKIs resistance mechanism, BRAF fusion is a huge clinical challenge, indicate the importance of further research.
A multi-center phase II study of toripalimab with chemotherapy in patients with EGFR mutant advanced NSCLC patients resistant to EGFR TKIs: Efficacy and biomarker analysis.
Authors: Ren Shengxiang , Zhang Jie , Zhao Yanqiu , Mu Xiaoqian , Zhou Jianying , Bao Zhang , Fan Yun , Xu Yanjun , Shu Yongqian , Guo Renhua , Liu Xiaoqing , Wang Hong , Zhang Helong , Deng Lin , Ma Ningqiang , He Jianxing , Zhang Yalei , Zhou Caicun ,   Shanghai Junshi Biosciences
Published: May 2020

e21618 Background: Immune checkpoint blocker (ICB) monotherapy showed a lack of response in advanced NSCLC patients with EGFR mutations. This Phase II study aimed to evaluate the efficacy and safety of toripalimab, a humanized PD-1 mAb plus platinum doublets chemotherapy in EGFR mutant advanced NSCLC patients, who developed resistance to 1st/2nd generation of EGFR TKIs and without T790M mutation. Methods: Patients received toripalimab (240 or 360 mg) intravenously combined with carboplatin (AUC = 5) and pemetrexed (500mg/m2) on day 1, Q3W, for up to 6 cycles, followed by toripalimab and pemetrexed maintenance until disease progression or unacceptable toxicity. Efficacy was evaluated every six weeks according to RECIST v1.1. PD-L1 expression (JS311 assay) and co-mutation status by whole exome sequencing were further analyzed. Results: From Apr 2018 to March 2019, 40 patients were enrolled from 8 centers in China. The median age was 57 years with 53% female, 57.5% EGFR exon19 deletion and 42.5% L858R mutation. By the cutoff date of Jan 2, 2020, 20 partial response and 15 stable disease were observed (ORR 50% and DCR 87.5%) with a median DOR of 7.0 months. The median PFS was 7.0 months and the median OS was still not reached. 52.6% (20/38) patients were PD-L1+ (TPS≥1%) and had numerically higher ORR (60% vs 39%, p= 0.33) and longer PFS (median 8.3 vs 5.7 months, p= 0.61) than PD-L1- patients. Co-mutations analysis revealed common genetic alternations including TP53 (79%), RB1 (18%), ERBB2 (15%), PIK2CA (12%), CDKN2A (12%), HDAC9 (12%) and MET (9%). Patients with TP53 co-mutation responded significantly better in ORR than TP53 wild type patients (62% vs 14%, p= 0.04) . Most frequent TRAE included leukopenia (78%), neutropenia (70%), anemia (70%), ALT elevation (48%), AST elevation (48%) and nausea (48%). Grade 3+ TRAE occurred in 55% patients, including neutropenia (43%), leukopenia (20%) and anemia (13%). Dose delay due to TRAE occurred in 40% patients while 10% patients discontinued treatment due to TRAE. Conclusions: Toripalimab in combination with chemotherapy showed promising anti-tumor activity with a manageable safety profile for advanced NSCLC patients with EGFR mutations refractory to TKI therapies. Patients with PD-L1+ tumor biopsy or TP53 co-mutation preferentially responded to the combination. A randomized phase III trial is ongoing to further validate the finding in this study (NCT03924050). Clinical trial information: NCT03513666.
Real-world outcomes after second-line treatment in non-small cell lung cancer (NSCLC) patients treated with immunotherapy.
Authors: Marmarelis Melina Elpi , Hwang Wei-Ting , Yang Yu-Xiao , Ciunci Christine Agnes , Singh Aditi Puri , Aggarwal Charu , Cohen Roger B. , Langer Corey J. , Mamtani Ronac , Bauml Joshua 
Published: May 2020

e21620 Background: In patients (pts) with advanced non-small cell lung cancer (NSCLC), national guidelines recommend against retrial of immunotherapy (IO) if there is disease progression on IO in the 1st-line (1L). However, optimal 2nd-line (2L) therapy after 1L IO remains unclear and there is significant practice variation. We compared outcomes of 2L approaches after 1L IO or chemoimmunotherapy (chemoIO). Methods: This retrospective cohort study utilized the Flatiron Health EHR-derived de-identified advanced NSCLC database. The study population included pts with disease progression on 1L IO or chemoIO and who subsequently received 2L therapy. Pts with targetable alterations were excluded. We defined the exposure by type of 2L therapy (IO, chemoIO, chemo). Multivariate covariates included age, sex, race, 1L progression-free survival (PFS) and PDL1 level. Median overall survival (mOS) and median real-world PFS (mPFS, based upon abstraction of clinician documentation) times were estimated from Kaplan-Meier curves. A multivariate Cox proportional hazard model computed hazard ratios (HRs) to assess the effectiveness of 2L treatment. Results: 532 NSCLC pts received 1L IO and a 2L therapy, of which 393 (74%) received 1L IO and 139 (26%) received 1L chemoIO. Among 1L IO patients, 2L therapies included chemo (315 (80%)), IO (39(10%), 18/39 (46%) switched IO), and chemoIO (39(10%)). Among 1L chemoIO patients, 2L therapies included: chemo (121 (87%)), IO (8(6%), 6/8 switched IO) and ChemoIO (10 (7%), 8/10 changed chemo used). All pts who received 2L ChemoIO continued the same IO agent. Demographics were well balanced between 2L groups except for higher PDL1 level in the IO-based groups and older age in the IO alone group. There was no statistically significant difference in mPFS or mOS between 2L IO and non-IO containing regimens (Table), nor were there differences among patients switching IO agents in the 2L (multivariate p interaction = 0.2 (PFS), 0.06 (OS)) (Table). Conclusions: Despite national guidelines against this practice, a small proportion of pts in routine care receive 2L IO-based therapies after disease progression on 1L IO or chemoIO. We found similar outcomes between IO and non-IO based 2L therapies after progression on 1L IO or chemoIO. [Table: see text]
IMpower110: Clinical safety in a phase III study of atezolizumab (atezo) monotherapy (mono) vs platinum-based chemotherapy (chemo) in first-line non-small cell lung cancer (NSCLC).
Authors: Jassem Jacek , Herbst Roy S. , de Marinis Filippo , Cadranel Jacques , Csőszi Tibor , Isla Dolores , Chen Gongyan , Syrigos Konstantinos N. , Cortinovis Diego , Hida Toyoaki , Mocci Simonetta , Phan See , Enquist Ida , Patel Hina , Villalobos Monette , Wen Xiaohui , Deng Yu , Kuriki Hiroshi , Spigel David R. , Giaccone Giuseppe 
Published: May 2020

e21623 Background: IMpower110 evaluated atezo mono in PD-L1–selected, chemo-naive patients (pts) with nonsquamous (nsq) or squamous (sq) NSCLC. At the interim analysis, IMpower110 met its primary OS endpoint, with a statistically significant and clinically meaningful improvement for atezo vs chemo in TC3 or IC3 wild-type ( EGFR/ALK-negative) pts. We report on the safety profile of atezo vs chemo in IMpower110. Methods: 572 pts with stage IV nsq or sq NSCLC, PD-L1 expression ≥ 1% on TC or IC and ECOG PS 0-1 were randomized 1:1 to receive atezo (1200 mg IV q3w) or chemo (4 or 6 21-day cycles). In the chemo arm, nsq pts received cisplatin (cis) 75 mg/m2 or carboplatin (carbo) AUC 6 + pemetrexed (pem) 500 mg/m2 IV q3w; sq pts received cis 75 mg/m2 + gemcitabine (gem) 1250 mg/m2 or carbo AUC 5 + gem 1000 mg/m2 IV q3w. Safety was assessed in all treated pts (safety evaluable [SE] population [pop]), regardless of PD-L1 expression or EGFR/ALK status. AEs were summarized per MedDRA v22.0 and severity graded per NCI CTCAE v4.0. Immune-mediated AEs (imAEs) were defined per a sponsor-specified list of terms, regardless of whether the events led to systemic glucocorticoid, endocrine therapy, or other immunosuppressants use. Results: At data cutoff (Sep 10, 2018) within the ITT pop, treatment (tx) was ongoing in 90 (atezo: 31.6%) and 25 (chemo: 8.7%) pts, with 13.7 mo of follow-up. Within the SE pop (atezo: n = 286, chemo: n = 263), atezo pts had longer tx exposure (5.3 mo) vs chemo pts (pem, 3.5 mo; gem, 2.6 mo; carbo, 2.3 mo; cis, 2.1 mo). Atezo had a favorable safety profile vs chemo (table); safety data were consistent with data from a pooled atezo mono pop. imAEs occurred in 40.2% (atezo) and 16.7% (chemo) of pts and were Grade (Gr) 3-4 in 6.6% and 1.5%, respectively. Conclusions: Atezo was better tolerated than chemo and imAEs were generally low grade. Overall, the safety experience with atezo mono in IMpower110 was consistent with its known safety profile; no new safety signals were identified. Clinical trial information: NCT02409342. [Table: see text]
IMpower150: Exploratory efficacy analysis in patients (pts) with bulky disease.
Authors: Jotte Robert M. , Batus Marta , Bernicker Eric , Copur Mehmet Sitki , Kirshner Eli , Koh Han A. , Kozloff Mark , Sabbath Kert D. , Subramanian Janakiraman , Yu Wei , Nowicki Michael , Bara Ilze , Finley Gene Grant 
Published: May 2020

e21637 Background: In the Ph 3 IMpower150 study (NCT02366143), 1L treatment (tx) with atezolizumab (A) + bevacizumab (B) + carboplatin + paclitaxel (CP; ABCP) significantly improved PFS and OS vs B + CP (BCP) in pts with chemotherapy-naive metastatic (met) nsq NSCLC. As pts with high tumor burden or large size (bulky disease) have poor survival outcomes, an exploratory analysis was conducted to determine whether pts with bulky disease in IMpower150 could derive benefit from ABCP. Methods: 1202 pts (ITT population) were randomized 1:1:1 to ABCP, atezo + CP (ACP) or BCP arms. Doses were given q3w: A, 1200 mg; B, 15 mg/kg; C, AUC 6 mg/mL/min; P, 200 mg/m2. Disease burden subgroups (high or low) were defined using the 3rd quartile of the sum of the longest diameter (SLD) of the target lesions or median number (no.) of met sites at baseline (BL). Exploratory efficacy analyses included PFS, OS, ORR, time to response (TTR) in these subgroups; safety was also assessed. Outcomes are reported for pts enrolled in the ABCP vs BCP arms. Results: Per 3rd quartile SLD (108 mm), 91 ABCP and 85 BCP pts had high disease burden. Per median no. of met sites (median = 2), 210 ABCP and 190 BCP pts had high disease burden. BL characteristics were generally balanced between ABCP and BCP in high disease burden subgroups. With a minimum follow-up of 32.4 mo (data cutoff: Sep 13, 2019), ABCP showed improved OS, PFS and ORR vs BCP in pts with high and low disease burden (Table). High disease burden did not impact TTR. The safety profile of ABCP was comparable between ITT-WT (no EGFR or ALK alterations) pts and high disease burden subgroups. Conclusions: A tx effect for OS, PFS and ORR was seen in pts with and without bulky disease when ABCP vs BCP was compared, regardless of the method used to define “bulky”; TTR was not affected in high disease burden pts. ABCP had a comparable safety profile in bulky disease and ITT-WT pts. ABCP may be a 1L tx option for pts with nsq NSCLC who have high disease burden. Clinical trial information: NCT02366143. [Table: see text]
Cancer cachexia syndrome in the prediction of outcome in patients with metastatic non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs): Results from a single-institution, prospective, observational study.
Authors: Mavroudis Dimitrios , Rounis Konstantinos , Makrakis Dimitrios , Georgiou Alexandra , Galanakis Nikolaos , Papadaki Chara , Vamvakas Lampros , Tsigkas Alexandros-Pantelis , Kontogianni Meropi , Gioulbasanis Ioannis , Agelaki Sofia 
Published: May 2020

e21644 Background: Cancer cachexia syndrome (CCS) is a multifactorial inflammatory syndrome affecting a large subset of patients (pts) with NSCLC which in preclinical models negatively impairs antitumor immunity. We conducted a prospective, observational study to investigate the effect of CCS and sarcopenia on the efficacy of ICIs in NSCLC. Methods: CCS was defined as weight loss of > 5% in the last 6 months or any degree of weight loss > 2% in combination with BMI < 20% or baseline skeletal muscle index at the level of the 3rd lumbar vertebra consistent with sarcopenia. Skeletal muscle index was calculated using slice-o-matic tomovision software in the abdominal CT scan before starting ICIs. Results: 83 pts were included in the analysis. Median follow up was 9.5 months. Median age was 66 years, 61.4% had non-squamous histology, 20.5% received ICIs as first and the remaining as second-line therapy. 20.5% of pts experienced partial response (PR), 31% had stable disease (SD) and 48.2% had disease progression (PD). Median progression-free survival (PFS) was 4.4 months and median overall survival (OS) was 10.33 months. 43.4% of the whole group were categorized as having CCS, whereas 63.3% of 30 pts evaluated using tomovision had sarcopenia. CCS negatively affected response rates (p = 0.003) but not response duration (p = 0.266). CCS was associated with reduced PFS (2.46 vs 5.77 months, p = 0.006) and OS (4.8 vs 14.53 months, p = 0.001). In the multivariate analysis, CCS independently predicted for shorter OS (HR = 2.01; CI: 1,14-3,54; p = 0.014). Sarcopenia was also associated with reduced OS (5.4 vs 17.9 months, p = 0.012). Analysis on the whole pt population will be presented at the conference. Conclusions: CCS is associated with lower response rates and independently predicts for shorter OS in pts with NSCLC treated with ICIs. Further research on CCS could better define its role as a potential biomarker and a research platform for maximizing immunotherapy efficacy.