bluuebunny/crossref_metadata_2025_split huggingface dataset:
Successful treatment of pulmonary lymphangitic carcinomatosis by anlotinib in 14 Chinese patients with advanced non-small cell lung cancer.
Authors: Fang Shencun , Cheng Wanwan , Zhang Yingming , Zhang Haitao , Li Si , Xiao Mingzhe 
Published: June 2021

e21064 Background: Pulmonary lymphangitic carcinomatosis (PLC) occurs in 6%-8% of intrathoracic metastases among malignant tumor. The median survival was only 2.0 months from time of pulmonary symptoms to death in cases during 2000-2018, which is a poor prognosis. Effective interventions were needed besides standard chemotherapy and symptomatic support. Anlotinib showed a critical effect on lymphangiogenesis, and lymphatic metastasis in mouse models of lung adenocarcinoma, it might be a therapeutic option for tumor lymphatic metastasis. In this study, we retrospectively analyzed the efficacy and safety of anlotinib for PLC in patients with Non-small Cell Lung Cancer (NSCLC). Methods: We retrospectively investigated NSCLC patients with PLC at our hospital between May 2018 and November 2020, who received anlotinib monotherapy or combined therapy for PLC. Data were analyzed for progression-free survival (PFS), overall survival (OS), objective response rate(ORR), disease control rate(DCR) and adverse events (AE). The impact of clinical and genomic factors on PFS and OS were also assessed. Results: A total of 14 patients were enrolled with a median age of 64 years. 10(71.4%) were male, 4(28.6%) has smoking history, 10(71.4%) of patients had a performance status of 2-3. 9, 3, 2 patients had TP53 mutation, EGFR mutation, ALK fusion respectively. 9(64.3%) patients received anlotinib monotherapy. Of 14 patients, 8 achieved partial response (PR), 5 presented stable disease (SD), 1 had progressed disease. The ORR and DCR were 57.1% and 92.9% respectively. The median PFS was 3.1 months (95% CI: 2.0-4.2), the median OS for 1, 2, ≥3 line were 13 months, 7.2 months, 5.2 months, respectively. Median PFS and OS (≥3 line) were significantly longer for patients with TP53-mutant tumors compared with those with TP53–wild-type tumors (median PFS: 7 vs. 1.1 months, median OS (≥3 line): 6.8 vs. 1.9 months). No difference of PFS and OS (≥3 line) was found between EGFR or ALK alteration and the corresponding wild type patients. The most frequently reported AEs were high blood pressure (11, 78.6%), hand foot syndrome (6, 42.9%), diarrhea (5, 35.7%), fatigue (4, 28.6%), hoarseness (3, 21.4%), proteinuria (2, 14.3%) and stomatitis (2, 14.3%). Conclusions: Anlotinib presented favorable efficacy in patients with pulmonary lymphangitic carcinomatosis and conferred considerable survival benefit compared with previous studies, especially in patients harboring TP53 mutations. The AEs were manageable. These indicated that anlotinib can be a promising therapeutic treatment of PLC. More clinical data is needed to validate this finding.
Spectrum of adipokines, batokines, myokines, and growth factors in blood serum of patients with various stages of lung cancer and with immunotherapy with PD-1/PD-L1 inhibitors.
Authors: Zlatnik Elena Yu. , Sagakyants Aleksandr B. , Kit Oleg I. , Shulgina Oksana G. , Kalabanova Elena A. , Teplyakova Maria A. , Vladimirova Liubov Yu , Storozhakova Anna E. , Novikova Inna A. , Kharagezov Dmitry A. , Milakin Anton G. , Konstantinova Yulia S. 
Published: June 2021

e21069 Background: Metabolites of the intestinal microbiota, including adipokines, batokins, and myokines, are involved in carcinogenesis, antitumor immune defense and ensuring the effectiveness of antitumor treatment, including chemotherapy and immunotherapy. Methods: The study included 100 patients with lung cancer (LC), 70% males and 30% females: stage I – 10%, II - 14%, III – 50%, IV – 26%. 21 patients (12 males and 9 females) received treatment with PD-1/PD-L1 inhibitors: stage I - 2 (9%), II - 1 (5%), III - 5 (24%), IV - 12 (62%). Therapy included atezolizumab and pembrolizumab – 9 patients each (43%), nivolumab – 3 (14%). Complete response was registered in 2 (9%), partial response in 5 (24%), stabilization - 4 (19%), progression - 8 (38%). One patient developed an immune-mediated adverse event (Guillain-Barré syndrome), so checkpoint inhibitors (CPI) were canceled. Serum levels of adipokines, myokines, batokines, and growth factors were determined by ELISA before and during treatment. The control group included 100 healthy donors. Results: Levels of VEGF and NGF were statistically significantly higher in patients with lung cancer than in donors, without differences in other parameters. Differences were revealed depending on the LC stage: leptin was higher in stages I and IV (Me 52.8 and 46.3 ng/ml, respectively) compared with stages II and III (Me 27.4 and 16.4 ng/ml, respectively) and with donors (Me 12.5 ng/ml). In stages III and IV, levels of VEGF increased (Me 504 and 473 pg/ml, respectively; in donors Me 239 pg/ml), while BDNF decreased (Me 2.7 and 0.4, respectively, in donors Me 12.6 μg/ml); NGF in stages I and II was not detected, unlike stages III and IV. Immunotherapy with CPI elevated levels of adiponectin (Me 12.5 and 16 μg/ml, respectively), and reduced levels of myostatin (Me 26.4 and 2.8 μg/ml, respectively) and NGF (Me 130 and 53 pg/ml, respectively). Only NGF could be regarded as a predictive factor of the response to CPI, since it was detected in high amounts only in patients with subsequent LC progression, while in patients with a positive response to treatment or stabilization, it was absent both before and after immunotherapy. Conclusions: Serum levels of some adipokines, myokines, batokins, and growth factors in LC patients differ depending on the cancer stage and the result of CPI immunotherapy; thus, NGF can be used as a predictor of the immunotherapy effectiveness. The study was performed with financial support from the Federal Medical and Biological Agency of Russia under contract No. 0373100122120000017 dated 20.05.2020.
Efficacy and safety of anti-EGFR monoclonal antibody (SCT200) as third-line or further treatment in advanced lung squamous cell cancer.
Authors: Dong Xiaorong , Wu Lin , Huang Dingzhi , Cheng Ying 
Published: June 2021

e21070 Background: Treatment strategies for advanced lung squamous cell cancer (LSCC) of third-line or further-line are limited. We assessed the efficacy and safety of recombinant anti-EGFR monoclonal antibody SCT200 in patients with advanced LSCC in a phase 1b study. Methods: Advanced LSCC Patients previously treated with at least two chemotherapy regimens were randomly assigned to intravenous injection of SCT200 9 or 12 mg/kg every week (QW) for a maximum of 6 cycles, followed by 12 or 15 mg/kg every two weeks (Q2W). The primary endpoint was objective response rate (ORR). The secondary endpoint was progression free survival (PFS), overall survival (OS) and safety. This study was registered at ClinicalTrials.gov (NCT03808701). Results: Between March 19, 2019 and October 19, 2019, a total of 25 patients were enrolled and 23 were included in the final analysis (10 low dose [9mg/kg] and 13 high dose [12mg/kg]). The median age was 57 years old, and 21 (91.3%) patients were males. 22 patients (95.6%) had ECOG performance status of 1, and 17 (74%) were stage IV. The baseline characteristics were similar between the two dose groups. While no patients were evaluated as complete response or partial response, 5 and 6 patients achieved stable disease in the 9mg/kg and 12mg/kg dose groups respectively. However, the mOS was 5.96m (2.14 ̃ NR) and 9.59m (2.86 ̃ NR) in the low and high dose groups respectively. The mPFS was 2.23 (0.23 ̃ 5.26) and 1.38 (1.25 ̃ 3.02) in each group. The most common grade ≥3 treatment-related AEs were hypomagnesemia (13%), rash (13%) and anemia (4.3%). Conclusions: In this trial, a clinical benefit in OS was observed in the high dose group. SCT200 was shown to be safe and well tolerated in all patients. Our study indicated that SCT200 could serve as a potential single treatment or in combination with other therapy for advanced LSCC. Clinical trial information: NCT03808701. [Table: see text]
The prognostic role of body-mass index (BMI) for advanced EGFR positive non-small cell lung cancer (NSCLC) patients treated with osimertinib.
Authors: De Giglio Andrea , Di Federico Alessandro , Donati Giada , Deiana Chiara , Nuvola Giacomo , Fragomeno Benedetta , Sperandi Francesca , Melotti Barbara , Gelsomino Francesco , Ardizzoni Andrea 
Published: June 2021

e21078 Background: In advanced EGFR-mutated non-small cell lung cancer (NSCLC) population, osimertinib represents the standard of care both for EGFR tyrosine kinase (TK) inhibitor-naive patients and for those with EGFR-mutated NSCLC harboring the T790M mutation and progressed following prior EGFR-TK inhibitor. No clear data supports the relationship between body mass index (BMI) and osimertinib's efficacy. Methods: We conducted a single-center, retrospective study including advanced EGFR-mutated NSCLC patients treated with Osimertinib as second or subsequent lines from February 2016 to December 2020. We examined survival outcomes according to BMI among a BMI-low group ( < 25 Kg/mq2) and BMI-high group (≥25 Kg/mq2). Results: A total of 37 consecutive patients received osimertinib as second- or subsequent line at our Institution. The mean age was 63.5 years (range 34-83 years), 24 (65%) patients were female, 16 (59%) were former or never smokers, and 25 (67%) had three or more metastatic sites at the start of therapy. The BMI-low group includes 25 (67%) patients and the BMI-high group 12 (33%), respectively. Globally, the median overall survival (mOS) was 29.9 mo. (95% CI, 18.2 – NR) and median progression-free survival (mPFS) was 17.5 mo. (95% CI, 15.7-33.3). The median follow-up was 32.5 mo. (IQR, 13.35-42.06). The mPFS was 21.0 mo. (95 CI, 16.8 – NR) within the BMI-low group and 16.8 mo. (95 CI, 4.4 – NR) within the BMI-high group, respectively (p = 0.03). Analogously, the mOS within the BMI-low group was 29.9 mo. (95 CI, 20.8 – NR) versus 18.2 mo. (95 CI, 11.7- NR) for the BMI-high group (p = 0.01). A BMI ≥25 Kg/mq2 constituted an independent risk factor for mortality [HR 3.99, (95 CI, 1.2 – 13.2), p 0.02] at multivariate analysis, including also age and number of metastatic sites. The BMI-high group showed a non-significant tendency to progression [HR 2.76, (95 CI, 0.9 - 8.3), p 0.06] at the same multivariate analysis. Conclusions: In our experience, a BMI ≥25 Kg/mq2 negatively influenced survival outcomes of 2nd-line osimertinib' treated NSCLC patients. More comprehensive studies are warranted to confirm these findings.
An exploratory clinical study of gefitinib combined with anlotinib in the first-line treatment of stage ⅢB-Ⅳ EGFR gene mutant non-small cell lung cancer patients with slow progress.
Authors: Wang Pengyuan 
Published: June 2021

e21089 Background: Anlotinib is a new type of small molecule anti-angiogenic drug that can inhibit the activity of a variety of tyrosine kinase receptors. Based on the initial efficacy of the combination of anti-angiogenic drugs and EGFR-TKIs and a clearer definition of people who are sensitive to EGFR-TKIs treatment, this study explores the slow progress of first-line use of gefitinib in patients with non-small cell lung cancer slowly progress, the efficacy and safety of combined Anlotinib. Methods: Fifteen patients with first-line non-small cell lung cancer who received gefitinib treatment and slowly progressed after enrolled in Xuchang Central Hospital, 15 received anlotinib(12mg/d from day 1 to day 14 in a 21-day cycle) combined with gefitinib（250mg /d） treatment until the disease progressed or died or was intolerable Adverse events. The primary endpoint was the progression-free survival(PFS), and the secondary endpoints were objective response rate (ORR), disease control rate( DCR) and safety. Results: As of January 4, 2021, a total of 15 patients have been enrolled and 14 patients can be evaluated. 0CR, 5PR, 8SD, 1PD. The median progression-free survival was 13.3 months (95% Cl, 3.71-4.89), and the most common adverse reactions were Grade 1, including hypertension (42.86%) and fatigue (21.42%). No higher-grade adverse reactions. Conclusions: Gefitinib combined with Anlotinib Hydrochloride Capsules is safe, effective and well tolerated when the first-line treatment of EGFR gene mutant non-small cell lung cancer patients progresses slowly.
Network meta-analysis (NMA) of immuno-oncology (IO) monotherapy as first-line (1L) treatments (txs) for advanced non-small cell lung cancer (NSCLC) with PD-L1 expression ≥50%.
Authors: Freemantle Nicholas , Xu Yingxin , Wilson Florence , Guyot Patricia , Chen Chieh-I , Keeping Sam , Konidaris Gerasimos , Chan Keith , Kuznik Andreas , Atsou Kokuvi , Glowienka Emily , Stow Lisa , Pouliot Jean-Francois , Gullo Giuseppe , Rietschel Petra , Rizvi Naiyer A. 
Published: June 2021

e21091 Background: For advanced NSCLC patients (pts) with high (≥50%) PD-L1 expression, effective IO mono options with survival benefits are approved (pembrolizumab mono, current standard of care) and emerging (cemiplimab). In a recent Phase 3 trial, cemiplimab, a high-affinity, highly potent human PD-1 inhibitor approved for tx of advanced cutaneous squamous cell carcinoma, demonstrated significantly improved overall survival (OS) and progression-free survival (PFS) vs chemotherapy (CT) in advanced NSCLC pts with PD-L1 ≥50%. A systematic literature review and NMA were conducted to identify/compare the efficacy/safety from randomized controlled trials (RCTs) for cemiplimab vs pembrolizumab or other IO mono published 2010–19. Methods: Relevant RCTs were identified by searching Embase, MEDLINE, Cochrane, and conference proceedings with predefined search strategies according to ISPOR, NICE, and PRISMA guidelines. An NMA with time-varying hazard ratios (HRs) was performed for OS and PFS. Analyses were conducted for objective response rate (ORR), Grade (G) 3–5 all-cause adverse events (AE), G3–5 immune-mediated AE (IMAE) and discontinuation due to AEs (DAE). Fixed-effect models were used due to limited evidence. Results with standard constant HRs and various sensitivity analyses were conducted to account for differences in RCT designs and other txs. Results: The feasibility assessment determined that EMPOWER-Lung 1, KEYNOTE-024, and KEYNOTE-042 trials were eligible. IMpower110 was excluded since an incompatible PD-L1 assay (SP142) was used for pt selection. For 1L advanced NSCLC with PD-L1 ≥50%, cemiplimab was associated with significantly greater PFS and ORR, and comparable OS, G3–5 AEs, IMAEs, and all-cause DAEs vs pembrolizumab (Table). At 2 yrs, numerically more pts receiving cemiplimab vs pembrolizumab were alive (59% vs 49%) and significantly more were alive w/o progression (37% vs 18%). Conclusions: In advanced NSCLC pts with PD-L1 ≥50%, cemiplimab mono demonstrated significant improvements in PFS and ORR, and comparable OS, safety/tolerability vs pembrolizumab.[Table: see text]
Interaction effect between mutational events on predicting efficacious immunotherapy in nonsquamous NSCLC: Results from 1,083 patients.
Authors: Zhang Fan , Zhao Lei , Li Tao , Xu Yu , Li Chengcheng , Wang Guoqiang , Cai Shangli , Hu Yi , Wang Jinliang 
Published: June 2021

e21100 Background: Despite that the biomarkers of single mutational events predicting efficacy of immune checkpoint inhibitors (ICIs) have been intensively studied in non-squamous NSCLC, the interaction effects between mutations on prediction were scarcely investigated due to the limited sample size. Deeper understanding of these inter-relations could optimize the prediction model and provide insights for basic research on anti-tumor immunity. Methods: In total, 1083 patients with non-squamous NSCLC were included. 288 patients with both PFS and OS data receiving monotherapy from the MSKCC, DFCI, and SNCC cohorts were included in the training set-1. 304 and 294 patients from the POPLAR/OAK cohort treated with atezolizumab or docetaxel were included in the training set-2 and the control set respectively. Validation set-1 and validation set-2 respectively consists of 104 patients receiving monotherapy with only OS data and 93 patients treated with combination therapy from the MSKCC cohort. Risk models using single mutations (uni-model) and both single mutations and interactions (inter-model) were developed via multivariable Cox proportional hazards regression model. Results: By cross-validation in training set-1/2, five single mutational events, including mutations of EGFR, STK11, PTPRD, members in PI3K pathway, and members in HRR pathway, and five interactions ( EGFR* PI3K pathway, TP53* KRAS, TP53* ERBB4, cell cycle pathway*HRR pathway, and PI3K pathway*chromatin remodeling pathway) were identified as predictive biomarkers. The score of inter-model exhibited higher correlation with immunotherapeutic PFS in the training sets, compared to the uni-model ( Dxy: 0.173 vs. 0.139). Uni-score low was moderately associated with longer OS in the validation set-1 (HR = 0.62, 95% CI 0.35-1.08, P = 0.092), and PFS in the validation set-2 (HR = 0.32, 95% CI 0.18-0.60, P < 0.001). Inter-score low showed better predictive utility in the validation set-1 (HR = 0.53, 95% CI 0.30-0.94, P = 0.030), and the validation set-2 (HR = 0.23, 95% CI 0.10-0.50, P < 0.001). On the contrary, inter-score low was associated with worse PFS and OS in the control set, indicating that inter-score low might be a negative prognostic biomarker, but positive predictive biomarker to efficacious immunotherapy. Conclusions: Our study suggests that the predictive biomarkers might not be similarly predictive in every single subpopulation, and they might be merely valid under certain circumstances, which is termed by “interaction effect”. Given this, the future researches probing into immunotherapeutic predictor should focus on the mutual influence between distinct biomarkers, for instance, adding an interaction term in the Cox proportional hazards regression model.
Economic evaluation of crizotinib, alectinib, ceritinib, and brigatininb in anaplastic lymphoma kinase positive (ALK+) non-small cell lung cancer (NSCLC) as second-line treatment.
Authors: Alkhatib Nimer S. , Choi Briana , Halawah Hala , Calamia Matthias , Gulick Dexter , Manasrah AlMothana , Alkhdour Odai , McBride Ali , Abraham Ivo 
Published: June 2021

e21104 Background: Crizotinib, alectinib, ceritinib, and brigatinib are approved as second line treatment for ALK+ NSCLC. Crizotinib was the first ALK inhibitor for first line therapy approved by Food and Drug Administration (2011) then ceritinib (2014), alectinib (2015), and brigatinib (2017) were approved as second line drugs. Following more data, these agents were approved as the first line therapy (2017 for ceritinib and alectinib; 2020 for brigatinib). These remain as a treatment option in patients who fail the first line therapy. Cost-effectiveness/utility analyses were conducted to assess clinical efficacy with varying costs of the agents. Methods: A three state Markov model were assumed (progression free, progression and death). Progression free survival (PFS) curves were digitized and fitted with exponential function. US payer perspective, a lifetime horizon, and discount rate of 3% were applied. Drug costs were Redbook wholesale acquisition cost. Other costs included were monitoring, adverse events and disease progression from published data (US$ 2020). Adverse events reported >5% in patients were included. Measured outcomes were PFS life years (PFSLY) and quality adjusted life years (PFSQALY). Crizotinib was the reference drug. Incremental cost-effectiveness and utility ratios (ICER/ICUR) of PFSLY and PFSQALY gained (PFSLYG, PFSQALYG) and lost were estimated. Base case (BCA) and probabilistic sensitivity analyses (PSA) were conducted. Results: Crizotinib was the reference drug for the following outcomes. For alectinib, with the decremental cost of -$14,653 (-$14,712), the incremental PFSLY of 0.16 (0.16) and PFSQALY of 0.05 (0.05) resulted in an ICER / PFSLYG of -$89,337 (-$88,604) and an ICUR / PFSQALYG of -$269,835 (-$266,510). For brigatinib, with the decremental cost of -$14,975 (-$14,954), the incremental PFSLY of 0.01 (0.01) and PFSQALY of ̃0.01 (0.02) yielded an ICER / PFSLYG of -$1,982,962 (-$1,431,631) and an ICUR / PFSQALYG of -$2,140,534 (-$570,538). For ceritinib, with the incremental cost of $7,590 ($7,514), there were decremental PFSLY of -0.01 (-0.01) and PFSQALY of -0.03 (-0.03). Conclusions: As second line treatment, crizotinib, ceritinib, and brigatinib had comparable PFSLYs and PFSQALYs while alectinib had the most PFSLY and PFSQALY and the lowest cost. Therefore, alectinib is the most cost-effective treatment for treating ALK+ NSCLC as the second line therapy.[Table: see text]
Atezolizumab in first-line treatment of metastatic nonsquamous non-small cell lung cancer in the real-world setting.
Authors: De Castro Javier , Campos Balea Begoña , Perez Parente Diego , Polito Letizia , Lawrance Marcus , Ruiz Gracia Pedro , Adler Leah , Marina Arroyo Marta , Socinski Mark A. 
Published: June 2021

e21112 Background: The phase III IMpower150 study showed efficacy benefits with atezolizumab in combination with bevacizumab, carboplatin and paclitaxel (ABCP; arm B) as first-line (1L) treatment for patients (pts) with metastatic non-squamous (nsq) NSCLC. The FDA approved this regimen for these pts (with no EGFR or ALK mutations [WT]) on December 2018. However, to date there is limited evidence on its use in real life. This study aimed to explore the use of ABCP in the real-world setting and to describe the characteristics of early adopters (those who received ABCP in 1L). Methods: Data were extracted from the Flatiron Health database (US population). Pts with advanced stage IIIB/IV nsq NSCLC at diagnosis receiving ABCP regimen in any line were eligible for the study. Finally, early adopters were selected. Results: A total of 67 pts received the ABCP regimen in 1L. Baseline characteristics for these pts and comparisons with the IMpower150 population are summarized in Table. Real-world (rw) response in the WT group ( n = 49; 6 pts were excluded due to EGFR mutations and 12 because minimum follow-up was not reached) was similar to that of the IMpower150 series (rwRR: 55.1% [40.2-69.3] vs. 63.5% [58.2-68.5]), despite the WT population being older with a higher proportion of ECOG PS = 1. In patients who would have met the IMpower150 inclusion criteria ( n = 24), rwRR was 70.8% (48.9-87.4). Conclusions: The ABCP regimen has been adopted in the real-world setting. In terms of efficacy, response rates and current PFS data were in line with trial results, despite the population being unselected and having a worse clinical profile. Longer follow-up is required for rwOS data. vs. arm B IMpower150 results.[Table: see text]