bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of EGFR-TKIs monotherapy versus TKI plus chemotherapy as first-line treatment in EGFR mutant lung adenocarcinoma with liver metastases.
Authors: Wang Huijuan , Li Mengmeng , Zhang Mina , guo Wei Zhang , Yan Xiangtao , Ma Zhiyong , Xing Ruyue 
Published: June 2021

e21099 Background: Liver metastasis is one of the most reasons for the poor prognosis of patients with advanced lung cancer. Seeking for active and effective treatment measures is very important for these patients. At present, the first-line standard treatment of the advanced NSCLC with EGFR mutation is EGFR-TKIs monotherapy. However, its efficacy is poor in the advanced non-small cell lung cancer with EGFR mutation and liver metastases. The objective of this study is to evaluate the efficacy of EGFR-TKIs plus chemotherapy in patients with EGFR mutation of advanced non-small cell lung cancer with liver metastases. Methods: The clinical data of a total of 384 advanced NSCLC patients with EGFR mutation positive who were admitted to The Affiliated Cancer Hospital of Zhengzhou University/Henan Cancer Hospital from February 2017 to June 2020 were retrospectively analyzed. There were 75 patients with liver metastases. Patients were divided into two groups, and accepted EGFR-TKIs monotherapy or EGFR-TKIs plus chemotherapy, respectively. All patients treatment response were evaluated by the RECIST1.1 Response evaluation criteria in solid tumors.Progression free-survival (PFS) were also analyzed. Results: In the study, 75 patients were finally screened. There were 37 patients in the EGFR-TKIs monotherapy group and 38 patients in the TKI plus chemotherapy group. The median follow-up time was 23.0 months. At the latest follow-up date (2021-01-01), 57 patients had disease progression and 35 patients had died. Comparing with EGFR-TKIs monotherapy,the first-line PFS of EGFR-TKI plus chemotherapy group was longer, and the median PFS was 12.7 months VS 7.4 months (P = 0.018).The ORR of primary lung lesions was no significant difference between these two groups（65.8%VS 51.4% P = 0.204), and DCR (97.4% VS 94.6% P = 0.981) also had no difference between two groups（P > 0.05）. ORR of liver metastases in the EGFR-TKIs plus chemotherapy group was significantly higher than EGFR-TKIs monotherapy group ORR (65.8%VS 40.5%，P = 0.028). Conclusions: In advanced NSCLC patients with EGFR mutation and liver metastases, comparing with EGFR-TKIs monotherapy, taking EGFR-TKIs plus chemotherapy as first-line treatment had longer PFS, and better efficacy on liver lesions.
Economic evaluation of crizotinib, alectinib, ceritinib, and brigatinib in treatment naïve anaplastic lymphoma kinase positive (ALK+) non-small cell lung cancer (NSCLC).
Authors: Choi Briana , Alkhatib Nimer S. , Halawah Hala , Calamia Matthias , Gulick Dexter , Manasrah AlMothana , Alkhdour Odai , McBride Ali , Abraham Ivo 
Published: June 2021

e21102 Background: Crizotinib was approved by the FDA (2011) as the first ALK inhibitor for ALK+ NSCLC as the first line drug. This was followed by the approval as second line treatment of ceritinib (2014), alectinib (2015) and brigatinib (2017); and, following more data, now also as first line therapies in ALK+ NSCLC. With varying costs and clinical benefits for progression free survival (PFS), cost effectiveness/utility analyses were conducted. Methods: A 3 state Markov model was built including progression free, progression and death. PFS and overall survival curves were digitized and exponential functions were fit the curves for extrapolation beyond trial follow up. A lifetime horizon, US payer perspective, and a discount rate of 3% were applied. Drug costs were based on Redbook Wholesale Acquisition Cost while costs of adverse events, monitoring, disease progression were from literatures (US$ 2020). Adverse events reported at > 5% were included. Crizotinib was used as reference treatment. PFS life years (PFSLY), quality adjusted life years (PFSQALY), incremental cost-effectiveness and utility ratios (ICER/ICUR) of PFSLY and PFSQALY gained (PFSLYG, PFSQALYG) were estimated in base case (BCA) and probabilistic sensitivity analyses (PSA). Results: Crizotinib was the reference drug in the following estimations. For alectinib, at incremental cost of $7,789 (PSA $7,719), the incremental PFSLY of 1.10 (1.10) and PFSQALY 1.07 (1.07) yielded an ICER of $7,109 ($7,030) / PFSLYG and an ICUR of $7,278 ($7.197) / PFSQALYG. For ceritinib, at incremental cost of $88,688 ($88,450), the incremental PFSLY of 1.02 (1.02) and PFSQALY of 1.01 (1.01) resulted in an ICER of $86,970 ($86,729) / PFSLYG and an ICUR of $87,472 / PFSQALYG. For brigatinib, at incremental cost of $84,680 ($83,986), the incremental PFSLY of 1.01 (1.01) and PFSQALY of 1.02 yielded an ICER of $83,774 ($83,073) / PFSLYG and an ICUR of $82,666 ($81,976) / PFSQALYG. Conclusions: Ceritinib had the highest lifetime cost and comparable PFSLY and PFSQALY to brigatinib. However, alectinib reported the highest PFSLY and PFSQALY gained while having lower costs than ceritinib and brigatinib, therefore being the most cost-effective treatment for naïve ALK+ NSCLC.[Table: see text]
Integration of proteomic and clinical data for the prediction of response to immune checkpoint inhibitor therapy in non-small cell lung cancer.
Authors: Shaked Yuval , Harel Michal , Lahav Coren , Jacob Eyal , Sela Itamar , Yahalom Galit , Elon Yehonatan , Sharon Ofer , Kamer Iris , Bar Haim , Dicker Adam P. , Bar Jair , Katzenelson Rivka , Wolf Ido , Gottfried Maya , Abu-Amana Mahmud , Agbarya Abed , Nechushtan Hovav , Moskovitz Mor Tal , Zer Alona 
Published: June 2021

e21110 Background: Immune checkpoint inhibitor (ICI) therapy represents one of the most promising cancer treatments to date. However, despite unprecedented rates of durable response, only a small proportion of patients benefits from this approach. Major efforts are therefore required to characterize treatment resistance mechanisms, as well as to identify reliable biomarkers for response. We have previously shown that in response to various types of cancer therapy, including ICIs, the host may induce pro-tumorigenic processes that can promote therapy resistance. Here we examined systemic host-response proteomic profiles in non-small cell lung cancer (NSCLC) patients, aiming to discover biomarkers for response to ICI therapy and to unravel underlying resistance mechanisms. Methods: As part of our ongoing PROPHETIC clinical trial (NCT04056247), plasma samples were obtained at baseline (T0) and early-on treatment (T1; following the first treatment) from 120 NSCLC patients receiving ICI therapy. Proteomic profiling of the plasma samples was performed using proximity-extension assay (PEA) technology; validation was carried out for a fraction of the samples using ELISA-based arrays. To identify a proteomic signature that predicts clinical outcome, machine learning algorithms were applied following a random separation of the cohort into a discovery set and a validation set. Results: A proteomic signature predictive of response to treatment was identified and validated. Bioinformatic analysis identified potential mechanisms of resistance based on differentially expressed proteins associated with pro-tumorigenic biological processes. Statistical analysis of the clinical data identified multiple novel differential clinical parameters between responders and non-responders, either at baseline or by comparing T0 to T1, which may suggest host-mediated effects. Conclusions: Our study demonstrates the potential clinical utility of analyzing the host response to ICI therapy, in particular for the discovery of novel predictive biomarkers for NSCLC patient stratification. Clinical trial information: NCT04056247.
Phase II, noncomparative, open label, multicenter, study of osimertinib, in patients with locally advanced or metastatic EGFR mutated, T790M undetectable or unknown non-small cell lung cancer (Stage IIIB-IV) after no immediate prior EGFR TKI (OSIRIS study).
Authors: Soto Parra Hector J. , Noto Laura , Verderame Francesco , Galetta Domenico , Barbieri Vito , Ferrau Francesco , Migliorino Maria Rita , Catino Annamaria , Aiello Marco M. , Capelletto Enrica , Ricciardi Serena , Spinnato Francesca , Tassone Pierfrancesco , Morelli Anna Maria , Latteri Fiorenza , Gozzo Lucia , Valerio Oriana , Avola Rossana , Novello Silvia 
Published: June 2021

e21116 Background: Osimertinib (OSI) is a potent irreversible EGFR TKI approved for 1st line therapy advanced EGFR+ NSCLC and for 2nd line T790M+ pts. The AURA trial showed promising results even in pts with T790M- NSCLC after no immediate prior OSI in locally advanced or metastatic EGFR+ NSCLC, T790M undetectable or unknown, after 1st line EGFR TKI and subsequent chemotherapy. Methods: This phase II trial was performed to investigate the role OSI in locally advanced or metastatic EGFR+ NSCLC, T790M undetectable or unknown, after 1st line EGFR TKI (1 or 2 generation) and subsequent chemotherapy. Eligible pts (M or F, > 18 years, ECOG 0-2) received OSI (80 mg/day) until disease progression or unacceptable toxicity. Objective response rate (ORR) was the primary endopoint. Assuming a 10% attrition rate, 90 pts were planned to be enrolled according to the Optimal Simon’s 2 stage design. In the first stage, 32 pts were planned to be accrued, and if ≤ 3 responses were observed the study would be stopped. Otherwise, 49 additional pts were planned to be accrued. The null hypothesis would have been rejected if ≥ 12 responses were observed. This design yields a type I error rate of 0.05 and 80% power. Results: From May 2017 to October 2020, a total of 54 pts were enrolled (17 M and 37 F, mean age 66 years). The study was stopped early due to an extremely slow enrolment rate. However, the ORR of 31.5% (95% CI 19.5% - 45.5%) was significantly higher than the null hypothesis of 9% (p<0.0001). 17 pts obtained a partial response and 20 a stable disease with an overall disease control rate of 68.5%. Median PFS was 9 mos and median OS was 15 mos. Forty-one pts experienced at least 1 adverse event (51.8% treatment related), more than 90% Grade 1 or 2, the most common being diarrhea. Conclusions: Despite early termination and incomplete recruitment, the treatment with OSI in pts with undetectable or unknown T790M showed a significant ORR and a PFS in line with results in T790M+. Currently, OSI represents the preferred option in naïve pts with EGFR+ NSCLC, regardless of T790M status and for pts who progress the recommended subsequent therapies include local therapy, continuing OSI or chemotherapy; in this new scenario, our results confirm that OSI rechallenge in subsequent line after chemotherapy should be explored. This research was conducted with support from AstraZeneca. Clinical trial information: 2016-002555-17.
Feasibility of RECIST-based real-world tumor response assessment in metastatic non-small cell lung cancer patients.
Authors: Tran Nguyet , Fu Alan , Izano Monika A. , Toland Liz , Hilbelink Ryan , Tu Huakang , Hsu Hil , Sommers Chris , Rioth Matthew J. , Brown Thomas D. 
Published: June 2021

e21121 Background: Treatment response to anti-cancer therapies for advanced lung cancer is usually assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST), which is not generally applied in real-world settings. With real-world evidence increasingly being used to support promising treatment, this study evaluated the feasibility of assessing real-world lung cancer response by RECIST-based measurement of lesions on archived radiologic films and assessed its concordance with treatment response based on oncologist narratives in electronic health record (EHR). Methods: This retrospective study included 30 randomly selected metastatic non-small cell lung cancer (mNSCLC) patients diagnosed between January 2015 and December 2019 from the Syapse Learning Health Network of US community health systems. Eligible patients were ≥18 years, histologically confirmed mNSCLC; no other malignancy within 2 years prior to diagnosis; initiated index systemic treatment subsequent to progression on a platinum or anti-PD(L)-1-containing therapy; and had a baseline scan followed by at least one additional scan during the index period. Patients were followed from the initiation of index treatment until the initiation of a post-index line of treatment, death, or date of last contact, whichever occurred first. Tumor response was established using response documented in the medical oncologists’ narratives and compared to a radiologist’s assessment of archived images using RECIST v1.1 criteria. Best overall response was characterized as complete or partial response (CR/PR), stable disease (SD), progressive disease (PD), and not evaluable (NE). Results: The median age at mNSCLC diagnosis was 62 years; 22/30 (73%) were male; 28/30 (93%) were White and 2/30 (7%) were Black. Of the 22/30 (73%) patients with a documented Eastern Cooperative Oncology Group performance status, 21 (95%) had a status of 0 or 1. Patients had a median of 8 months follow-up with the majority surviving (63%) until the end of study. Table shows good concordance of best overall response between medical oncologist-reported and radiologist re-assessed responses; CR/PR was 67%, SD 79% and PD 80%. Causes of discordance were lack of CR/PR confirmation in medical oncologists’ narratives, absence of narratives, or presence of clinical symptoms. Conclusions: This study is an important step in demonstrating the potential to approximate real-world RECIST-based treatment response using EHR abstraction of oncologists’ documentation. Future studies should validate this approach, and improve upon it, by exploring additional real-world data elements as surrogates for clinically relevant responses to anti-cancer therapies. [Table: see text]
Albumin-bilirubin grade as a significant prognostic factor in patients with non-small cell lung cancer treated with anti-PD-1-based therapy: A multicenter retrospective study.
Authors: Takamori Shinkichi , Takada Kazuki , Shimokawa Mototsugu , Toyokawa Gouji , Shimamatsu Shinichiro , Hirai Fumihiko , Tagawa Tetsuzo , Okamoto Tatsuro , Hamatake Motoharu , Tsuchiya-Kawano Yuko , Otsubo Kohei , Inoue Koji , Yoneshima Yasuto , Tanaka Kentaro , Okamoto Isamu , Nakanishi Yoichi , Mori Masaki 
Published: June 2021

e21125 Background: Albumin-bilirubin (ALBI) grade is calculated from albumin and bilirubin values as continuous variables, allowing an accurate evaluation of liver function. Some studies showed that ALBI grade was a prognostic and predictive biomarker for the efficacy of chemotherapy in cancer patients. However, no report has examined the association between ALBI grade and outcome in patients with non-small cell lung cancer (NSCLC) treated with anti-programmed cell death-1 (PD-1)-based therapy. Methods: We retrospectively enrolled 452 patients with advanced or recurrent NSCLC treated with anti-PD-1-based therapy (nivolumab or pembrolizumab monotherapy or pembrolizumab combination therapy) between 2016 and 2019 at three medical centers in Japan. With reference to previous reports, ALBI score was calculated using the formula (log10 (total bilirubin [mg/dL] x 17.1) x 0.66) + (albumin [g/dL] x 10 x −0.085), and the score was stratified as grade 1 (≤ −2.60), grade 2 (more than −2.60 to ≤ −1.39), and grade 3 (more than −1.39). We examined the clinical impact of ALBI grade on outcome in patients with NSCLC receiving anti-PD-1-based therapy using Kaplan–Meier survival analysis with the log-rank test and Cox proportional hazards regression analysis. Results: Of the 452 patients, 158 (35.0%) patients were classified as grade 1, 271 (60.0%) as grade 2, and 23 (5.0%) as grade 3. ALBI grade was strongly correlated with performance status (PS), clinical stage, and body mass index, and mutation status ( P < 0.0001, P = 0.0077, P = 0.0050, and P = 0.0302, respectively). The Kaplan–Meier curves showed that ALBI grade was significantly associated with progression-free survival (PFS) and overall survival (OS) ( P < 0.0001 and P < 0.0001, respectively). Multivariate analyses showed that PS ( P = 0.0044), combination therapy of anti-PD-1 and chemotherapy ( P = 0.0004), programmed cell death-ligand 1 (PD-L1) expression status ( P < 0.0001), and ALBI grade ( P < 0.0001) were independent prognostic factors for PFS. Multivariate analyses also showed that PS ( P = 0.0008), combination therapy of anti-PD-1 and chemotherapy ( P = 0.0066), PD-L1 expression status ( P = 0.0006), and ALBI grade ( P < 0.0001) were independent prognostic factors for OS. In the subgroup analysis, ALBI grade effectively stratified PFS and OS regardless of PD-L1 expression status. Conclusions: We report for the first time that ALBI grade was an independent prognostic factor for PFS and OS in patients with advanced or recurrent NSCLC receiving anti-PD-1-based therapy. These findings should be validated prospectively.
Impact of KRAS mutational variant on response to immunotherapy in metastatic NSCLC.
Authors: Kuang Shelley , Lau Sally C. M. , Sharma Kieran , Lee Juehea , Ryan Malcolm Isaiah , Schmid Sabine , Bradbury Penelope Ann , Liu Geoffrey , Shepherd Frances A. , Tsao Ming Sound , Leighl Natasha B. , Sacher Adrian G. 
Published: June 2021

e21127 Background: KRAS alterations constitute the most common driver mutations in metastatic non-small cell lung cancers (mNSCLC) and occur in approximately 30% of patients. KRAS mutational subtype as well as the presence of co-mutations has been associated with altered activation of downstream signaling pathways in preclinical models. We hypothesize that different KRAS G12C mutational subsets will be associated with variable clinical outcome and response to therapy. To this end, we have performed a retrospective analysis of survival and treatment outcomes by KRAS mutation subtype (G12C vs non-G12C). Methods: A review of KRAS-mutated mNSCLC patients treated with immunotherapy between 2013 and 2020 was conducted. Patient demographics, smoking status, KRAS mutational subtype, co-mutations and PD-L1 status were collected. Overall response rate (ORR) and progression-free survival (PFS) were analyzed in each subgroup. Results: 98 KRAS mutant mNSCLC patients were treated with immune checkpoint inhibitors (ICI): 37% with a KRAS G12C mutation, 62% with a non-G12C mutation. Patients with a G12C mutation were more likely to be of Caucasian ancestry (86% vs 56%; p = 0.01) whereas all other characteristics were similar between the groups including smoking history, PD-L1 expression ≥50% (61% vs 40%) and the presence of a TP53 co-mutation (48% vs. 54%); all p > 0.05. Treatment patterns were similar between the groups, with PD-1 inhibitor monotherapy given in 86% vs 79% of KRAS G12C and non-G12C patients. Overall response rate was 51% vs 27% in G12C vs non-G12C (p = 0.03). PFS was superior in G12C mutants (19.6 months vs 4.0 months), even after adjusting for smoking history, TP53 co-mutation status and PD-L1 expression (adjusted HR 0.51; p = 0.02). In subgroup analyses, the superiority in PFS was driven by the G12C mutants with high PD-L1 expression (n = 19): 26.8 months in G12C, PD-L1 high vs 4.7 months in G12C, PD-L1 low vs. 4.7 months in KRAS transversion mutations, PD-L1 high vs 4.0 months in transversion mutations, PD-L1 low vs. 3.0 months in transition mutations; p < 0.001. Conclusions: The presence of a KRAS G12C mutation is associated with improved ORR and PFS after treatment with ICI compared to non-G12C mutations in mNSCLC. The greatest benefit in PFS was observed in the subgroup with G12C mutation and high PD-L1 expression. Differential activation of downstream signaling associated with specific KRAS codon 12 mutation variants may modulate the composition of the tumor immune microenvironment thereby contributing to the variable response to immunotherapy. Further understanding on these molecular mechanisms may direct the development of new treatment strategies in KRAS mutant lung cancers.
The low advanced lung cancer inflammation index to predict poor prognosis of patients with metastatic non-small cell lung cancer.
Authors: Lu Ping , Ma Yifei , Kai Jindan , Wang Jun , Yin Zhucheng , Xu Hongli , Li Xinying , Liang Xin , Wei Shaozhong , Liang Xinjun 
Published: June 2021

e21132 Background: Inflammation plays a crucial role in cancers, in which the advanced lung cancer inflammation index (ALI) is considered to be a potential factor reflecting systemic inflammation. This work aimed to explore the prognostic value of ALI in metastatic non-small cell lung cancer (NSCLC) and classify patients according to their potential risks and different prognosis. Methods: Non-small cell lung cancer patients with stage IV were included in this retrospective study who were diagnosed pathologically in Hubei Cancer Hospital from June 2012 to December 2013. Combined with relevant imaging data and exfoliative cytology, patients with non-small cell lung cancer were staged according to the eighth edition of TNM staging criteria for non-small cell lung cancer. We screened 318 patients who met the inclusion and exclusion criteria requirements. The clinicopathological and therapeutic data of the patients were collected through medical records, including age, sex, smoking and drinking, tumor site, tumor family history, histology, metastatic site, chemotherapy, radiotherapy, anti-VEGF therapy and EGFR-TKI therapy. The formula of ALI is body mass index (BMI, Kg / m2) × serum albumin (Alb, g / dl) / neutrophil-lymphocyte ratio (NLR). Categorical variables were analyzed by chi-square test or Fisher’s exact test. The OS rates was analyzed by Kaplan–Meier method and plotted with R language. Multivariate Cox proportional hazard model was used to analyze the relationship between ALI and OS. The nomogram based on the Multivariable Cox regression was establish, and the Harrell consistency index (C-index) was used to evaluate the predictive performance of the Cox regression model. Results: According to the optimal cut-off value determined by X-tile software, patients were divided into two groups: ALI < 32.6 and ALI ≥ 32.6 and the median OS in the high ALI group were better than those in the low ALI group (39.97 vs 19.23 months, p < 0.01). Local or distant metastases and some distant metastasis sites are related to prognosis. Multivariable Cox regression model confirmed that ALI (HR: 1.39; 95%CI: 1.03-1.89; P = 0.03) and chemotherapy (HR: 0.67; 95%CI: 0.49- 0.91; P = 0.01) were independent prognostic factors for OS in patients with metastatic non-small-cell lung cancer. Conclusions: The results of our study indicates that patients with low ALI tend to have lower OS in metastatic NSCLC, and ALI can serve as an effective prognostic factor for metastatic NSCLC patients.