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Simple Summary: This study analyzes real-world outcomes for advanced, non-oncogene addicted non-small cell lung cancer patients treated with atezolizumab monotherapy following platinum-based chemotherapy, based on data from two academic institutions in Serbia. Progression-free survival did not significantly differ between patients receiving atezolizumab as a second, third, or later line of therapy, indicating consistent efficacy across treatment lines. Additionally, the number of prior chemotherapy cycles had no significant impact on progression-free survival, suggesting that a higher prior treatment burden did not compromise atezolizumab effectiveness. Importantly, a good ECOG performance status emerged as the strongest predictor of prolonged progression-free survival, highlighting the importance of patients' health status at treatment initiation. Immune checkpoint inhibitors (ICIs) like atezolizumab have improved outcomes in advanced non-small cell lung cancer (NSCLC) patients, especially in the second-line setting after progression on platinum-based chemotherapy. However, access to ICIs remains limited in many developing nations. This study evaluated the efficacy of atezolizumab as a second-line versus later-line treatment for advanced NSCLC patients in Serbia. Methods: This retrospective study involved 147 advanced NSCLC patients treated with atezolizumab following progression on prior platinum-based chemotherapy at two academic centers in Serbia. Data on demographics and clinical, pathological, and molecular characteristics were collected. Median progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method, and multivariable Cox proportional hazards regression identified outcome predictors. Results: The median PFS was 7.13 months, and median OS was 38.6 months. The overall response rate (ORR) was 15%, with a disease control rate (DCR) of 57.9%. No significant PFS differences were observed between patients treated with atezolizumab in the second line versus later lines. Patients with good performance status (ECOG 0–1) had significantly better PFS compared to those with poorer status (12.03 vs. 1.63 months, p < 0.0001). Conclusions: Atezolizumab is effective in both second-line and later-line settings for advanced NSCLC, particularly in patients with good performance status. This highlights the importance of patient selection based on performance status, as well as the need for wider access to ICIs in resource-limited regions. [ABSTRACT FROM AUTHOR]

Despite breakthroughs of immunotherapy synergistically combined with blockade of vascular endothelial growth factor receptor, several patients with advanced non‐small cell lung cancer (NSCLC) experience non‐response or followed relapse. Organized lymphoid aggregates, termed tertiary lymphoid structures (TLSs), are found to be associated with improved response to immunotherapy. Here, we explore the landscapes of TLSs in tumour tissues from a real‐world retrospective study. Our investigation showed that with a median follow‐up of 11.2 months, the ORR was 28.6% (18/63, 95% CI 17.9–41.3) and the median PFS was 6.1 (95% CI 5.5–6.6) months in NSCLC patients treated with PD‐1 blockade combined with anlotinib. By multiplex immunofluorescence (mIF) analysis, spatially, more TLSs and high CD20+ B‐cell ratio in TLSs were associated with higher ORR. High density of intratumoral CD8+ T cells showed better ORR and PFS. The numbers of CD8+ T cells with a distance within 20 μm and 20–50 μm between tumour cells were higher in responders than non‐responders. But responders had significantly higher TLSs within 20 μm rather than within 20–50 μm of tumour cells than non‐responders. The inflamed immunophenotyping occupied higher proportions in responders and was associated with better PFS. Besides, tumour cells in non‐responders were found more temporal cell‐in‐cell structures than responders, which could protect inner cells from T‐cell attacks. Taken together, landscape of TLSs and proximity architecture may imply superior responses to PD‐1 blockade combined with anlotinib for patients with advanced non‐small cell lung cancer. [ABSTRACT FROM AUTHOR]

Objective: To conduct a comprehensive evaluation of PD-1 inhibitors for the treatment of advanced non-small cell lung cancer on the market in China, using A Quick Guideline for Drug Evaluation and Selection in Chinese Medical Institutions (Second Edition), and to provide a reference for the selection of and decision-making on clinical drugs in hospitals. Method: The Sanzhi drug evaluation and selection system was used to evaluate the PD-1 inhibitors for the treatment of advanced non-small cell lung cancer on the market in China, according to five characteristics: pharmaceutical characteristics, efficiency, safety, economy, and others. Results: Based on the above evaluation criteria, the scores of all PD-1 inhibitors were above 61 points. The main difference among the five characteristics were efficiency and economy. The difference between the other characteristics was relatively small. Sintilimab injection had the highest score due to the advantages among characteristics except the other attributes. Nivolumab injection (100 mg/10 mL (10 mg/mL)) had the lowest total score due to its low effectiveness and economy scores. Conclusion: PD-1 inhibitors are effective therapeutic drugs for immunotherapy in patients with advanced nonsmall cell lung cancer. Different PD-1 inhibitors have different advantages in clinical treatment. The comprehensive evaluation of PD-1 inhibitors for the treatment of advanced non-small cell lung cancer on the market in China through A Quick Guide for Drug Evaluation and Selection of Chinese Medical Institutions (Second Edition) can provide a basis for drug selection and scientific, reasonable, and safe drug use in medical institutions. [ABSTRACT FROM AUTHOR]

Introduction: Advanced or metastatic non-small cell lung cancer (NSCLC) is associated with significant symptom burden. It is important to understand the impact of these disease-and treatment-related symptoms on patients' daily lives and explore from a patient perspective what constitutes a meaningful change in NSCLC symptoms. Methods: Patient experience of advanced or metastatic NSCLC was explored in this prospective, non-interventional qualitative research study recruiting patients from the United States (US). Interviews were conducted to explore the most important symptoms, daily life impacts, and patients' perspectives of what constitutes meaningful change when considering their current symptoms versus 6-12 months prior, based on the Patient Global Impression of Severity (PGI-S) and Patient Global Impression of Change (PGI-C) items. Results: Between February and April 2022, 19 US-based patients with Stage IV NSCLC were recruited; 95% were female, 63% were White, 79% had been diagnosed >1 year prior, and 63% were receiving targeted therapy. Over half the patients indicated their most important symptoms were fatigue, shortness of breath, and cough. Patient differentiation between whether symptoms were disease- or treatment-related lacked concordance, and often patients were unable to distinguish the two. The most frequently mentioned impacts of these symptoms on patients' daily lives were difficulty walking, sleep disturbance, anxiety/depression, impact on relationships, and difficulty doing daily tasks. Most patients considered a one-point change on the PGI-S or PGI-C to be meaningful based on rating their symptom severity at the time of the interview compared with 6-12 months before the interview. Conclusion: Based on their own symptom experience, patients with advanced or metastatic NSCLC indicated a one-point threshold for meaningful change, whether improvement or worsening. This suggests a one-point change on the PGI-S or PGI-C may be a potential anchor for patient-reported outcome (PRO) endpoints used in clinical trials. It is important to use PRO instruments that capture the symptoms and impacts identified as most important to patients. These findings highlight the importance of using qualitative methods to assess disease-related symptoms, treatment-related side effects, and the impacts on daily life for patients with advanced or metastatic NSCLC, underscoring how qualitative assessments can complement quantitative PRO instruments for evaluating clinical trials. [ABSTRACT FROM AUTHOR]

To investigate the effects of shenqi fuzheng injection combined with cisplatin and pemetrexed on tumor markers, helper T cell (Th) 1/Th2 cytokines and serum microRNA (miR)-29b and miR-221 in patients with advanced non-small cell lung cancer (NSCLC). 131 patients with advanced NSCLC who were admitted to Fujian Provincial Hospital from March 2020 to December 2022 were divided into control group (cisplatin and pemetrexed treatment, n=65) and study group (shenqi fuzheng injection combined with cisplatin and pemetrexed treatment, n=66) according to the random number table method. The efficacy, tumor marker levels, Th1/Th2 cytokines, serum miR-29b and miR-221 expression levels were compared between two groups, and the incidence of adverse reactions was observed. The objective remission rate (48.48%) and disease control rate (81.82%) in study group were higher than those in control group (29.23%) and (60.00%) (P<0.05). After treatment, carcinoembryonic antigen (CEA), cytokeratin 19 fragment (CYFRA21-1), Th2, interleukin-4 (IL-4), squamous cell carcinoma antigen (SCC-Ag) and miR-221 in study group were lower than those in control group (P<0.05). After treatment, γ-interferon (IFN-γ), Th1 and miR-29b in study group were higher than those in control group (P<0.05). There was no difference in the incidence of adverse reactions between two groups (P>0.05). Compare with chemotherapy alone, shenqi fuzheng injection can effectively reduce the level of tumor markers and improve the clinical efficacy in the treatment of advanced NSCLC patients, which may be relate to the improvement of immune function and the regulation of serum miR-29b and miR-221 expression levels. [ABSTRACT FROM AUTHOR]

Tumor mutational burden (TMB) and T‐cell receptor (TCR) might predict the response to immunotherapy in patients with non–small cell lung cancer (NSCLC). However, the predictive value of the combination of TMB and TCR was not clear. Targeted DNA and TCR sequencing were performed on tumor biopsy specimens. We combined TMB and TCR diversity into a TMB‐and‐TCR (TMR) score using logistic regression. In total, 38 patients with advanced NSCLC were divided into a discovery set (n = 17) and validation set (n = 21). A higher TMR score was associated with better response and longer progression‐free survival to immunotherapy in both the discovery set and validation set. The performance of TMR score was confirmed in the two external validation cohorts of 225 NSCLC patients and 306 NSCLC patients. Tumors with higher TMR scores were more likely to combine with LRP1B gene mutation (p = 0.027) and top 1% CDR3 sequences (p = 0.001). Furthermore, LRP1B allele frequency was negatively correlated with the top 1% CDR3 sequences (r = –0.55, p = 0.033) and positively correlated with tumor shrinkage (r = 0.68, p = 0.007). The TMR score could serve as a potential predictive biomarker for the response to immunotherapy in advanced NSCLC. [ABSTRACT FROM AUTHOR]

objective: To investigate the effects of shenmai injection combined with gemcitabine and cisplatin on tumor markers, T lymphocyte subsets and serum apoptotic molecules in patients with advanced non-small cell lung cancer (NSCLC). Results: 118 patients with advanced NSCLC who were admitted to our hospital from March 2020 to December 2022 were divided into combined group (n=59, treated with shenmai injection combined with gemcitabine and cisplatin) and control group (n=59, treated with gemcitabine and cisplatin ) by random number table method. The tumor marker level, T lymphocyte subsets and apoptotic molecules were compared between two groups. Compared with control group, cytokeratin 19 fragment (CYFRA21-1), carcinoembryonic antigen (CEA), sqamous cell carcinoma antigen (SCC), carbohydrate antigen 125 (CA125), B-cell lymphoma (Bcl-2), Survivin (Survivin), CD8+ were lower in combined group after treatment, and Bcl-2-related X protein (Bax) and CD3+, CD4+, CD4+ /CD8+ were higher (P<0.05). Conclusion: Shenmai injection combined with gemcitabine and cisplatin for the treatment of advanced NSCLC Patients, which can reduce tumor markers level, reduce the immunosuppression of patients, regulate serum apoptotic molecules level. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effects of anlotinib combined with sintilimab on serum angiogenesis factors, tumor markers, platelet/lymphocyte ratio (PLR), neutrophil/lymphocyte ratio (NLR) and lymphocyte/monocyte ratio (LMR) in advanced non-small cell lung cancer (NSCLC) patients. Methods: 84 advanced NSCLC patients were divided into control group (42 cases, treated with anlotinib) and study group (42 cases, treated with sintilizumab combined with anlotinib) according to the random number table method. The efficacy, serum tumor markers [cytokeratin 19 fragment antigen 21-1 (CYFRA21-1), carbohydrate antigen 125 (CA125) and carcinoembryonic antigen (CEA)], angiogenesis factors [vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF)], NLR, PLR, LMR were compared between two groups, the incidence of adverse reactions was observed. Results: Compared with control group post-treatment, the objective remission rate, disease control rate and LMR in study group were higher, and VEGF, bFGF, CA125, CYFRA21-1, CEA, NLR and PLR were lower (P<0.05). There was no difference in the total incidence of adverse reactions between two groups (P>0.05). Conclusion: Combined use of anlotinib and Sintilimab in the treatment of advanced NSCLC patients, which can reduce the level of tumor markers, inhibit NSCLC angiogenesis, and reduce inflammatory response. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effects of brucea javanica oil emulsion injection combined with cisplatin and paclitaxel (TP) regimen on tumor markers, serum tumor abnormal protein (TAP) and heat shock protein 90α(Hsp90α)in patients with advanced non-small cell lung cancer (NSCLC). Methods: A total of 100 patients with advanced NSCLC who were admitted to the Department of Respiratory, Respiratory Hospital Area of Brain Hospital Affiliated to Nanjing Medical University from March 2018 to March 2020 were included. Randomized number table method was used in the groups, among them, 50 cases in the study group were treated with on the basis of TP regimen combined with brucea javanica oil emulsion injection, and 50 cases in the control group were treated with TP regimen alone. Efficacy, serum tumor markers, TAP, Hsp90α and incidence of adverse reactions were compared in the two groups. After 3 years of follow-up, the cumulative survival rate in the two groups was analyzed by the survival curve. Results: The objective remission rate and disease control rate in the study group were higher than those in the control group (P<0.05). 4 cycles after treatment, carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC), TAP, cytokeratin 19 fragment (CYFRA21-1) and Hsp90α in the study group were lower than those in the control group(P<0.05). There was no difference in the incidence of adverse reactions in the two groups (P>0.05). The progression-free survival time (PFS) and overall survival time (OS) in the two groups were tested by LogRank, all had significant differences(P<0.05). Conclusion: Brucea javanica oil emulsion injection combined with TP regimen in the treatment of patients with advanced NSCLC can effectively regulate tumor markers and serum TAP and Hsp90α levels, and prolong the survival rate of patients. [ABSTRACT FROM AUTHOR]

Background: Front-line therapy with an EGFR tyrosine kinase inhibitor (TKI) is the standard of care for treating patients with advanced nonsquamous NSCLC with the common sensitizing EGFR exon 19 deletion and exon 21 L858R point mutations. However, EGFR TKI resistance inevitably develops. The optimal subsequent therapy remains to be identified, although platinum-containing chemotherapy regimens are often administered. Our objectives were to describe baseline characteristics, survival, and subsequent treatment patterns for patients with advanced nonsquamous NSCLC with EGFR exon 19 deletion or L858R mutation who received a platinum-based combination regimen after front-line EGFR TKI therapy. Methods: This retrospective study used a nationwide electronic health record-derived deidentified database to select adult patients with advanced nonsquamous NSCLC, evidence of EGFR exon 19 deletion or L858R mutation, and ECOG performance status of 0-2 who initiated platinum-containing chemotherapy, with or without concomitant immunotherapy, from 1-January-2011 to 30-June-2020 following receipt of any EGFR TKI as first-line therapy or, alternatively, a first- or second-generation EGFR TKI (erlotinib, afatinib, gefitinib, dacomitinib) as first-line therapy followed by the third-generation EGFR TKI osimertinib as second-line therapy. Data cut-off was 30-June-2022. The Kaplan-Meier method was used to estimate overall survival (OS) after initiation of pemetrexed-platinum (n=119) or any platinum-based combination regimen (platinum cohort; n=311). Results: The two cohorts included two-thirds women (65%-66%) and 57%-58% nonsmokers; median ages were 66 and 65 years in pemetrexed-platinum and platinum cohorts, respectively. Median OS was 10.3 months (95% CI, 8.1-13.9) from pemetrexed-platinum initiation and 12.4 months (95% CI, 10.2-15.2) from platinum initiation; 12-month survival rates were 48% and 51%, respectively; 260 patients (84%) had died by the end of the study. Conclusion: The suboptimal survival outcomes recorded in this study demonstrate the unmet need to identify more effective subsequent treatment regimens for patients with EGFR-mutated advanced nonsquamous NSCLC after EGFR TKI resistance develops. [ABSTRACT FROM AUTHOR]

To investigate the effect of zhengyuan capsule combine with anlotinib on efficacy, cancer-related fatigue and immune function in patients with advanced non-small cell lung cancer (NSCLC) after second-line treatment. 103 patients with advanced NSCLC who were progressed driver gene negative after second-line treatment in Jinling Hospital Affiliated to Medical School of Nanjing University from April 2020 to May 2023 were selected, and patients were divided into control group (treated with anlotinib, n=51) and study group (treated with zhengyuan capsules combine with anlotinib, n=52) by random number table method. The clinical efficacy, Piper fatigue scale, Karnofsky functional status score (KPS), serum tumor markers [cytokeratin 19 fragment antigen 21-1 (CYFRA21-1), carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA125)], immune function indicators [natural killer (NK) cells, T lymphocyte subsets: CD4+, CD8+, CD4+/CD8+] were compared between two groups, and the occurrence of adverse reactions during the treatment in two groups was observed. Compared with control group, the objective response rate (ORR) and disease control rate (DCR) in study group were higher (P<0.05). The Piper fatigue scale score in study group after treatment was lower than that in control group, KPS score was higher than that in control group. The decrease levels of serum tumor markers CYFRA21-1, CEA, and CA125 in study group were higher than those in control group (P<0.05), immune function indicators, the decrease rate of NK cells, CD4+, CD4+/CD8+ in study group was lower than those in control group, and the increase rate of CD8+ was lower than that in control group (P<0.05). There was no difference in the incidence of adverse reactions between two groups during treatment (P>0.05). Zhenyuan capsule combine with anlotinib can improve the clinical efficacy of advanced NSCLC patients with progression driver gene negative after second-line treatment, which can reducing the level of tumor markers, reducing cancer-related fatigue, improving quality of life and improving immune function. [ABSTRACT FROM AUTHOR]

Abstract Tumor mutational burden (TMB) and T‐cell receptor (TCR) might predict the response to immunotherapy in patients with non–small cell lung cancer (NSCLC). However, the predictive value of the combination of TMB and TCR was not clear. Targeted DNA and TCR sequencing were performed on tumor biopsy specimens. We combined TMB and TCR diversity into a TMB‐and‐TCR (TMR) score using logistic regression. In total, 38 patients with advanced NSCLC were divided into a discovery set (n = 17) and validation set (n = 21). A higher TMR score was associated with better response and longer progression‐free survival to immunotherapy in both the discovery set and validation set. The performance of TMR score was confirmed in the two external validation cohorts of 225 NSCLC patients and 306 NSCLC patients. Tumors with higher TMR scores were more likely to combine with LRP1B gene mutation (p = 0.027) and top 1% CDR3 sequences (p = 0.001). Furthermore, LRP1B allele frequency was negatively correlated with the top 1% CDR3 sequences (r = –0.55, p = 0.033) and positively correlated with tumor shrinkage (r = 0.68, p = 0.007). The TMR score could serve as a potential predictive biomarker for the response to immunotherapy in advanced NSCLC.

Abstract Background This study aimed to evaluate the efficacy and side effects of first-line afatinib treatment in a real-world setting in Vietnam. Methods This retrospective study was conducted across nine hospitals in Vietnam. Advanced epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) patients who received afatinib as first-line therapy between April 2018 and June 2022 were included, and patient medical records were reviewed. Key outcomes were overall response rate (ORR), time-to-treatment failure (TTF), and tolerability. Results A total of 343 patients on first-line afatinib were eligible for the study. EGFR exon 19 deletion (Del19) alone was detected in 46.9% of patients, L858R mutation alone in 26.3%, and other uncommon EGFR mutations, including compound mutations, in 26.8%. Patients with brain metastases at baseline were 25.4%. Patients who received 40 mg, 30 mg, and 20 mg as starting doses of afatinib were 58.6%, 39.9%, and 1.5%, respectively. The ORR was 78.1% in the overall population, 82.6% in the Del19 mutation subgroup, 73.3% in the L858R mutation subgroup, and 75.0% in the uncommon mutation subgroup (p > 0.05). The univariate and multivariate analyses indicate that the ORR increased when the starting dose was 40 mg compared to starting doses below 40 mg (83.9% vs. 74.3%, p = 0.034). The median TTF (mTTF) was 16.7 months (CI 95%: 14.8–18.5) in all patients, with a median follow-up time of 26.2 months. The mTTF was longer in patients in the common EGFR mutation subgroup (Del19/L858R) than in those in the uncommon mutation subgroup (17.5 vs. 13.8 months, p = 0.045) and in those without versus with brain metastases at baseline (17.5 vs. 15.1 months, p = 0.049). There were no significant differences in the mTTF between subgroups based on the starting dose of 40 mg and 0.05). The most common treatment-related adverse events (any grade/grade ≥ 3) were diarrhea (55.4%/3.5%), rash (51.9%/3.2%), paronychia (35.3%/5.0%), and stomatitis (22.2%/1.2%). Conclusions Afatinib demonstrated clinical effectiveness and good tolerability in Vietnamese EGFR-mutant NSCLC patients. In our real-world setting, administering a starting dose below 40 mg might result in a reduction in ORR; however, it might not have a significant impact on TTF.

Background: Tumor treating fields (TTF) was first approved for treatment of glioblastoma. Recently, the LUNAR study demonstrated that TTF + standard therapy (ST) extended survival in patients with advanced non-small cell lung cancer (NSCLC). This primary objective of this study is to analyze the cost-effectiveness of this treatment from the United States healthcare payers' perspective. Methods: A 3-health-state Markov model was established to compare the cost-effectiveness of TTF + ST and that of ST alone. Clinical data were extracted from the LUNAR study, supplemented by additional cost and utility data obtained from publications or online sources. One-way sensitivity analysis, probabilistic sensitivity analysis, and scenario analysis were conducted. The willingness-to-pay (WTP) threshold per quality-adjusted life-years (QALYs) gained was set to $150,000. The main results include total costs, QALYs, incremental cost-effectiveness ratio (ICER) and incremental net monetary benefit (INMB). Subgroup analyses were conducted for two types of ST, including immune checkpoint inhibitor, and docetaxel. Results: During a 10-year time horizon, the costs of TTF + ST and ST alone were $431,207.0 and $128,125.9, and the QALYs were 1.809 and 1.124, respectively. The ICER of TTF + ST compared to ST was $442,732.7 per QALY, and the INMB was -$200,395.7 at the WTP threshold. The cost of TTF per month was the most influential factor in cost-effectiveness, and TTF + ST had a 0% probability of being cost-effective at the WTP threshold compared with ST alone. Conclusion: TTF + ST is not a cost-effective treatment for advanced NSCLC patients who progressed after platinum-based therapy from the perspective of the United States healthcare payers. [ABSTRACT FROM AUTHOR]

Objective: To investigate the relationship between serum progastrin-releasing peptide (ProGRP), tumor-specific growth factor (TSGF) and the efficacy and prognosis of patients with epidermal growth factor receptor (EGFR) mutation-positive advanced non-small cell lung cancer (NSCLC). Methods: A total of 95 EGFR mutation positive advanced NSCLC patients treated with EGFR-tyrosine kinase inhibitors in Qingdao Traditional Chinese Medicine Hospital, Qingdao Hongdao People’s Hospital, Qingdao Jiaoyun Geriatric Hospital, Qingdao Chest Hospital from January 2017 to January 2020 were selected. All patients were divided into effective and ineffective groups according to the efficacy and the difference in serum ProGRP and TSGF between the valid and ineffective groups was detected by chemiluminescence and rate methods. EGFR mutation positive patients and median survival time,according to the mean of serum ProGRP (365.73±14.35) pg/mL, TSGF (147.88±27.73 pg/mL, 41 patients), high TSGF (147.88 U, 46patients), low ProGRP (＜365.73 pg/mL, 54 patients), and low TSGF (＜347.88 U/m L, 49 patients). Survival curves of EGFR mutation-positive advanced NSCLC patients with high/low serum ProGRP and TSGF levels were plotted using the Kaplan-Meier method. And the patients with EGFR mutation-positive advanced NSCLC were divided into death group (56 cases) and survival group (39 cases) according to the prognosis. Factors affecting the prognosis of EGFR mutation-positive advanced NSCLC patients were analyzed using univariate and multivariate Cox regression, and the predictive value of serum ProGRP and TSGF levels in EGFR mutation-positive advanced NSCLC patients was analyzed by using receiver operating characteristic (ROC) curves. Results: After 6weeks of treatment, the serum ProGRP and TSGF levels were higher in the ineffective group than in the effective group (P＜0.05). There were no cases lost to follow-up during follow-up, the objective response rate of 95 EGFR mutation-positive advanced NSCLC was70.53% (67/95), a 3-year overall survival rate of 41.05% (39/95), and a median survival time of 16.00 months. The Kaplan-Meier curve analysis showed that the overall survival rate and median survival time in the high ProGRP and high TSGF groups were lower than those in the low ProGRP and low TSGF groups (P＜0.05). Univariate and multivariate Cox regression analysis showed that, TNM stage IV,poor differentiation, elevated ProGRP and elevated TSGF were independent risk factors affecting the prognosis of patients with EGFR mutation-positive advanced NSCLC (P＜0.05). ROC curve analysis showed that, the area under the curve of serum ProGRP and TSGF levels in predicting the death of patients with EGFR mutation-positive advanced NSCLC was 0.879, which was greater than 0.765 and0.773 predicted by serum ProGRP and TSGF levels alone. Conclusions: Elevated serum ProGRP and TSGF levels are closely related to the efficacy and prognosis of patients with EGFR mutation-positive advanced NSCLC, and the combined detection of serum ProGRP and TSGF levels has a high predictive value for them. [ABSTRACT FROM AUTHOR]

Background and aim: Chinese herbal injection (CHI) is a widely used preparation for advanced non-small cell lung cancer (NSCLC) treatment to alleviate the adverse drug reactions and enhance the clinical efficacy of chemotherapy. However, its efficacy and safety in combination with platinum-based chemotherapy (PBC) remain poorly understood owing to the lack of high-level evidence in the face of a wide variety of CHIs. Therefore, in this study, we aimed to explore the efficacy and safety of CHIs in combination with PBC regimens in the treatment of mid- and advanced NSCLC. Methods: Systematic evaluation and meta-analysis were conducted as per the Preferred Reporting Project for Systematic Evaluation and Meta-Analysis Protocols (PRISMA-P). Seven databases were comprehensively searched for relevant randomized controlled trials (RCTs) through August 1, 2022. The quality of each study was evaluated based on the Cochrane Handbook for Systematic Reviews of Interventions. Statistical analysis was performed using Revman 5.3, with dichotomies expressed as risk ratio (RR) and 95% confidence interval (CI). Objective response rate (ORR) and disease control rate (DCR) were selected as the primary outcomes, with quality of life (QoL) and toxic side effects as secondary outcomes. Results: A total of 140 RCTs were included in this study. The results of the metaanalysis suggested that, compared with PBC alone, PBC combined with CHIs significantly improved the ORR (RR=1.35, 95% CI: 1.30-1.41, P<0.001), DCR (RR=1.15, 95% CI: 1.13-1.18, P<0.001) and QoL (RR=1.29, 95% CI: 1.24-1.33, P<0.001). Moreover, the combination treatment reduced chemotherapyinduced leukopenia (RR=0.69, 95% CI: 0.64-0.75, P<0.001), anemia (RR=0.70, 95% CI: 0.62-0.79, P<0.001), thrombocytopenia (RR=0.68, 95% CI: 0.62-0.75, P<0.001), nausea and vomiting (RR=0.69, 95% CI: 0.63-0.76, P<0.001), diarrhea (RR=0.59, 95% CI: 0.48-0.73, P<0.001), and constipation (RR=0.68, 95% CI: 0.54-0.86, P=0.001). Conclusion: According to the available evidence, CHIs in combination with PBC can improve clinical efficacy and reduce the toxic side effects in the treatment of advanced NSCLC. However, considering the study's limitations, more rigorous and high-quality studies are needed to further confirm the results. [ABSTRACT FROM AUTHOR]

Background: This study aimed to evaluate the efficacy and side effects of first-line afatinib treatment in a real-world setting in Vietnam. Methods: This retrospective study was conducted across nine hospitals in Vietnam. Advanced epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) patients who received afatinib as first-line therapy between April 2018 and June 2022 were included, and patient medical records were reviewed. Key outcomes were overall response rate (ORR), time-to-treatment failure (TTF), and tolerability. Results: A total of 343 patients on first-line afatinib were eligible for the study. EGFR exon 19 deletion (Del19) alone was detected in 46.9% of patients, L858R mutation alone in 26.3%, and other uncommon EGFR mutations, including compound mutations, in 26.8%. Patients with brain metastases at baseline were 25.4%. Patients who received 40 mg, 30 mg, and 20 mg as starting doses of afatinib were 58.6%, 39.9%, and 1.5%, respectively. The ORR was 78.1% in the overall population, 82.6% in the Del19 mutation subgroup, 73.3% in the L858R mutation subgroup, and 75.0% in the uncommon mutation subgroup (p > 0.05). The univariate and multivariate analyses indicate that the ORR increased when the starting dose was 40 mg compared to starting doses below 40 mg (83.9% vs. 74.3%, p = 0.034). The median TTF (mTTF) was 16.7 months (CI 95%: 14.8–18.5) in all patients, with a median follow-up time of 26.2 months. The mTTF was longer in patients in the common EGFR mutation subgroup (Del19/L858R) than in those in the uncommon mutation subgroup (17.5 vs. 13.8 months, p = 0.045) and in those without versus with brain metastases at baseline (17.5 vs. 15.1 months, p = 0.049). There were no significant differences in the mTTF between subgroups based on the starting dose of 40 mg and < 40 mg (16.7 vs. 16.9 months, p > 0.05). The most common treatment-related adverse events (any grade/grade ≥ 3) were diarrhea (55.4%/3.5%), rash (51.9%/3.2%), paronychia (35.3%/5.0%), and stomatitis (22.2%/1.2%). Conclusions: Afatinib demonstrated clinical effectiveness and good tolerability in Vietnamese EGFR-mutant NSCLC patients. In our real-world setting, administering a starting dose below 40 mg might result in a reduction in ORR; however, it might not have a significant impact on TTF. [ABSTRACT FROM AUTHOR]

Introduction: Currently, first-line immune checkpoint inhibitors (ICIs), including programmed cell death protein-1 (PD-1) inhibitors, are utilized as monotherapy in advanced non-small cell lung cancer (NSCLC) patients with high programmed death ligand-1 (PD-L1) expression (50%). Pre-treatment or post-treatment serum soluble PD-L1 (sPD-L1) has been identified as a potential biomarker for assessing ICI efficacy through fixed-point observations. However, existing studies on sPD-L1 changes have produced inconsistent results or have had sample sizes too small to detect clinically meaningful effect sizes. To elucidate the role of sPD-L1, we conducted a collaborative individual patient data metaanalysis of PD-1 inhibitor treatments. Methods: We conducted a thorough search of articles in PubMed via Medline, Embase, Scopus, and Cochrane databases from inception to October 20, 2023. Trials were deemed eligible if they contained individual datasets for advanced NSCLC patients, including data on overall survival (OS)/progression-free survival (PFS), as well as pre- and post-treatment sPD-L1 levels after 3-4 cycles of PD-1 inhibitor treatments. Our analysis focused on patients who completed 3-4 cycles of PD-1 inhibitor treatments. The primary outcome measure was OS/PFS, and we assessed changes in sPD-L1 concentration pre- and post-treatment through ELISA analyses. Results: From our search, we identified a potential seven trials, encompassing 256 patients. Among these, two trials with 26 patients met the criteria for inclusion in our primary analyses. Over a median follow-up period of 10 months, pooled univariate analysis revealed that increases in sPD-L1 levels during PD-1 inhibitor treatment were not associated with OS (HR = 1.25; CI: 0.52-3.02)/PFS (HR = 1.42; CI: 0.61-3.30) when compared to cases with sPD-L1 decreases. Subgroup analyses indicated that the impact of sPD-L1 changes on overall mortality/progression-related mortality remained consistent regardless of gender, age, or the type of treatment (nivolumab or pembrolizumab). Conclusion: Our findings suggest that changes in sPD-L1 levels during PD-1 inhibitor treatment do not significantly influence the prognosis of advanced NSCLC patients, regardless of gender, age, or treatment type. Continuous monitoring of sPD-L1 may not offer significant advantages compared to fixedpoint observations. [ABSTRACT FROM AUTHOR]

To investigate the relationship between serum osteopontin (OPN), wild-type p53-induced phosphatase 1 (Wip1), heat shock protein 90α (HSP90 α) and the sensitivity and prognosis of first-line chemotherapy in patients with advanced non-small cell lung cancer(NSCLC). 137 advanced NSCLC patients who received first-line chemotherapy in the First Affiliated Hospital of Hebei Medical University from January 2018 to January 2020 were selected, patients were divided into chemotherapy insensitive group (38 cases) and chemotherapy sensitive group (99 cases) according to the efficacy of chemotherapy. Serum OPN and HSP90α levels were detected by enzyme-linked immunosorbent assay, and serum Wip1 mRNA level was detected by real-time fluorescence quantitative polymerase chain reaction. The factors affecting the sensitivity of first-line chemotherapy in advanced NSCLC patients were analyzed by multivariate Logistic regression analysis. After 3 years of follow-up, the prognosis of advanced NSCLC patients with high/low serum OPN, Wip1 mRNA and HSP90α levels after first-line chemotherapy were analyzed by Kaplan-Meier method. Compared with chemotherapy sensitive group, the levels of serum OPN, Wip1 mRNA and HSP90α in chemotherapy insensitive group were increased (P<0.05). Multivariate Logistic regression analysis showed that, poor differentiation, TNM stage IV and elevated serum OPN, Wip1 mRNA and HSP90α levels were independent risk factors affecting the sensitivity of first-line chemotherapy in advanced NSCLC patients (P<0.05). After 3 years follow-up, the overall survival rate of 137 advanced NSCLC patients was 15.33% (21/137). Kaplan-Meier survival curve showed that, the 3-year overall survival rate in high-level serum OPN, Wip1 mRNA and HSP90α group was lower than that in low-level serum OPN, Wip1 mRNA and HSP90α group (P<0.05). Serum OPN, Wip1 and HSP90α levels increase are associate with decrease sensitivity to first-line chemotherapy and poor prognosis in advanced NSCLC patients. [ABSTRACT FROM AUTHOR]

ObjectiveThis study aimed to evaluate the cost-effectiveness of two Chinese patent medicines, including Kang Ai injection and Shenqi Fuzheng injection with each combined with platinum-based chemotherapy as the first-line treatment for patients with advanced non-small cell lung cancer (NSCLC) in China.MethodsFrom Chinese healthcare system perspective, a three state Markov model with a cycle of 3 weeks and a 10-year horizon was constructed to derive the incremental cost-effectiveness ratio (ICER). Since only individual patient data of progression-free survival (PFS) of Kang Ai injection group can be obtained, we extrapolated median overall survival (mOS) of Kang Ai injection group and median progression-free survival (mPFS) and mOS of Shenqi Fuzheng injection group based on published literature and methods. Then survival curves were estimated by the method of declining exponential approximation of life expectancy (DEALE), which is based on the assumption that survival follows a declining exponential function. We performed one-way sensitivity analysis and probabilistic sensitivity analysis to test the robustness. Additionally, a scenario analysis was adopted to investigate the impact of using best-fitting distribution for PFS curve of Kang Ai injection group on the economic conclusion.ResultsThe base-case result indicated that Kang Ai injection group provided 0.217 incremental quality-adjusted life years (QALYs) at an incremental cost of $103.38 compared with Shenqi Fuzheng injection group. The ICER was $476.41/QALY, which was much lower than the willingness to pay threshold of one time the GDP per capita of China in 2022 ($12,070/QALY). Deterministic sensitivity analysis result showed that ICER was most sensitive to the changes in odds ratio (OR) value. The probabilistic sensitivity analysis confirmed the robustness of base-case analysis results. The scenario analysis result showed that by using Log-Normal distribution to fit the PFS curve of Kang Ai injection group and shortening the time horizon to 5 years, the ICER was $4,081.83/QALY, which was still much lower than the willingness to pay threshold.ConclusionKang Ai injection combined with platinum-based chemotherapy appeared to be more cost-effective for the treatment of advanced NSCLC than Shenqi Fuzheng injection combined with platinum-based chemotherapy.

BackgroundFront-line therapy with an EGFR tyrosine kinase inhibitor (TKI) is the standard of care for treating patients with advanced nonsquamous NSCLC with the common sensitizing EGFR exon 19 deletion and exon 21 L858R point mutations. However, EGFR TKI resistance inevitably develops. The optimal subsequent therapy remains to be identified, although platinum-containing chemotherapy regimens are often administered. Our objectives were to describe baseline characteristics, survival, and subsequent treatment patterns for patients with advanced nonsquamous NSCLC with EGFR exon 19 deletion or L858R mutation who received a platinum-based combination regimen after front-line EGFR TKI therapy.MethodsThis retrospective study used a nationwide electronic health record-derived deidentified database to select adult patients with advanced nonsquamous NSCLC, evidence of EGFR exon 19 deletion or L858R mutation, and ECOG performance status of 0-2 who initiated platinum-containing chemotherapy, with or without concomitant immunotherapy, from 1-January-2011 to 30-June-2020 following receipt of any EGFR TKI as first-line therapy or, alternatively, a first- or second-generation EGFR TKI (erlotinib, afatinib, gefitinib, dacomitinib) as first-line therapy followed by the third-generation EGFR TKI osimertinib as second-line therapy. Data cut-off was 30-June-2022. The Kaplan-Meier method was used to estimate overall survival (OS) after initiation of pemetrexed-platinum (n=119) or any platinum-based combination regimen (platinum cohort; n=311).ResultsThe two cohorts included two-thirds women (65%-66%) and 57%-58% nonsmokers; median ages were 66 and 65 years in pemetrexed-platinum and platinum cohorts, respectively. Median OS was 10.3 months (95% CI, 8.1-13.9) from pemetrexed-platinum initiation and 12.4 months (95% CI, 10.2-15.2) from platinum initiation; 12-month survival rates were 48% and 51%, respectively; 260 patients (84%) had died by the end of the study.ConclusionThe suboptimal survival outcomes recorded in this study demonstrate the unmet need to identify more effective subsequent treatment regimens for patients with EGFR-mutated advanced nonsquamous NSCLC after EGFR TKI resistance develops.

Objective: to evaluate the pharmacoeconomic efficiency of atezolizumab (inhibitor of programmed death ligand 1 (PD-L1)) in comparison with other checkpoint inhibitors (inhibitors of programmed cell death protein 1 (PD-1)) in patients with advanced non-small cell lung cancer (NSCLC) after previous chemotherapy in the current conditions of the Russian healthcare system.Material and methods. The study design was a retrospective analysis of publications and modeling. The previously performed pharmacoeconomic study was updated considering a decrease in the cost of pembrolizumab after the generic form was released on the market and actualization of calculated target population. Cost minimization analysis was carried out and the impact on the healthcare system budget was estimated when treating all NSCLC patients provided with PD-1/ PD-L1 inhibitors in the second and third lines of therapy with atezolizumab. For calculations, we used registered prices according to the state register of maximum selling prices and average weighted marginal wholesale markup according to the Federal Antimonopoly Service.Results. In the cost minimization analysis, atezolizumab showed greater clinical and economic efficiency, its use reduces costs by 28.6% over 3 years compared to nivolumab and by 8.8% compared to pembrolizumab in the second and third lines of NSCLC therapy. The budget impact analysis demonstrated that if all patients in the target group currently receiving various PD-1/PD-L1 inhibitors in the second and third lines of NSCLC therapy were initially provided with atezolizumab, it would reduce the budget load over 3 years by 11.6%, or by 722.4 mln rubles.Conclusion. The use of atezolizumab is pharmacoeconomically justified and feasible compared to nivolumab and pembrolizumab, even after a release of the generic version of the latter, and will reduce the costs of PD-1/PD-L1 inhibitors in the second and third lines of NSCLC therapy.

Objective To evaluate predictive factors affecting the short-term efficacy of PD-1 inhibitors in non-small cell lung cancer (NSCLC) and to construct a prediction model. Methods From October 2019 to November 2021, 221 patients with advanced NSCLC who met the inclusion criteria and were treated with PD-1 inhibitors were prospectively enrolled. Patients who were enrolled before May 1st, 2021 were included inthe modeling group (n=149), whereas those who enrolled thereafter were included in the validation group (n=72). The general clinical data of patients, information of the four TCM diagnoses were collected, and TCM syndrome elements were identified. R software version 4.0.4 was used in constructing a nomogram clinical prediction model of objective response rate. The predictive ability and discrimination of the model were evaluated and externally validated by using a validation group. Results After two to four cycles of PD-1 inhibitor therapy in 221 patients, the overall objective response rate was 44.80%. Multivariate logistic regression analysis of the modeling group showed that the TPS score (OR=0.261, P=0.001), number of treatment lines (OR=3.749, P=0.002), treatment mode (OR=2.796, P=0.019), qi deficiency disease syndrome elements (OR=2.296, P=0.043), and syndrome elements of yin deficiency disease (OR=3.228, P=0.005) were the independent predictors of the short-term efficacy of PD-1 inhibitors. Based on the above five independent predictors, a nomogram prediction model for the short-term efficacy of PD-1 inhibitors was constructed. The AUC values of the modeling and validation groups were 0.8317 and 0.7535, respectively. The calibration curves of the two groups showed good agreement between the predicted and true values. The mean absolute errors were 0.053 and 0.039, indicating that the model has good predictive performance. Conclusion The nomogram model constructed on the basis of the syndrome elements of Qi-deficiency disease and Yin-deficiency syndrome of TCM, as well as TPS score, number of treatment lines and treatment mode, is a stable and effective tool for predicting the short-term efficacy of PD-1 inhibitors in advanced non-small cell lung cancer.

Aim: Sarcopenia and skeletal muscle density (SMD) have been shown to be both predictive and prognostic marker in oncology. Advanced lung cancer inflammation index (ALI) has been shown to predict overall survival (OS) in small cell lung cancer (SCLC). Computed tomography (CT) enables skeletal muscle to be quantified, whereas body mass index (BMI) cannot accurately reflect body composition. The purpose was to evaluate the prognostic value of modified ALI (mALI) using CT-determined third lumbar vertebra (L3) muscle index beyond original ALI and see the interaction between sarcopenia, SMD, neutrophil-lymphocyte ratio (NLR), ALI and mALI at baseline and post 4 cycles of chemotherapy and their effects on OS and progress free survival (PFS) in patients with advanced non-SCLC (NSCLC). Methods: This retrospective study consisted of a total of 285 advanced NSCLC patients. The morphometric parameters such as SMD, skeletal muscle index (SMI) and fat-free mass (FFM) were measured by CT at the L3 vertebra. ALI was defined as BMI × serum albumin/NLR and mALI was defined as SMI × serum albumin/NLR. Results: Sarcopenia was observed in over 70% of patients across all BMI categories. Patients having sarcopenia suffered from a higher incidence of chemotherapeutic drug toxicities but this was not found to be statistically significant. Concordance was seen between ALI and mALI in the pre-treatment setting and this was statistically significant. A significant proportion of patients with poor ALI (90.9%), poor pre-chemotherapy mALI (91.3%) and poor post-chemotherapy mALI (89%) had poor NLR and each of them was statistically significant. Conclusions: In both univariate and multivariate analyses, this study demonstrated the statistical significance of sarcopenia, SMD, and mALI as predictive factors for OS. Additionally, sarcopenia and SMD were also found to be statistically significant factors in predicting PFS. These biomarkers could potentially help triage patients for active nutritional intervention for better outcomes.

Ferroptosis is a novel regulatory cell death characterized by iron dependence and mainly caused by the accumulation of lipid peroxides and reactive oxygen species in the cell. This process plays an important role in the development of many malignancies, and has been extensively studied in lung cancer, especially in antitumor therapy. In recent years, the role of ferroptosis in tumor immunotherapy has been gradually explored. Studies showed that targeting ferroptosis can improve the therapeutic efficacy of antitumor immunotherapy. In addition, immunotherapy and ferroptosis can work synergistically to enhance the effectiveness of antitumor therapy, suggesting a potential relationship between ferroptosis and immunotherapy and the possible reversal of immune drug resistance. This study aims to elucidate the characteristics of ferroptosis, and the role and potential clinical applications of ferroptosis in the antitumor immunotherapy of advanced non-small cell lung cancer. We also explore the role of some nanomaterials that target the onset of tumor ferroptosis in facilitating immunotherapy.

A large proportion of patients with non-small cell lung cancer (NSCLC) are diagnosed with metastatic and incurable advanced lung cancer at the time of discovery, so these patients are given no surgical opportunity and have a low 5-year survival rate. In the era of immunotherapy, many kinds of immune checkpoint inhibitors (ICIs) have been approved as the first/second-line treatment for patients with advanced NSCLC with negative driving genes and have been combined with radiotherapy as an important treatment strategy for patients with advanced NSCLC. The innovative strategy of combining radiotherapy and immunotherapy has shown feasibility as supported by practical evidence in clinical research. A preclinical experiment of observing the immune mechanism at the molecular and cellular levels preliminarily revealed the interaction among tumor, radiation, and immune system. This paper briefly reviews the progress of combined radiotherapy and immunotherapy in the treatment of advanced NSCLC with negative drvier genes.

María Presa,1 David Vicente,2 Antonio Calles,3 Laura Salinas-Ortega,1 Jaesh Naik,4 Luis F García,5 Javier Soto6 1Health Economics, Pharmacoeconomics and Outcomes Research Iberia (PORIB), Madrid, Spain; 2Medical Oncology Department, Hospital Universitario Virgen de Macarena, Sevilla, Spain; 3Medical Oncology Department, Hospital General Universitario Gregorio Marañon, Madrid, Spain; 4Health Economics, BresMed Health Solutions, Sheffield, UK; 5Oncology Medical, Pfizer, Madrid, Spain; 6Health Economics & Outcomes Research, Pfizer, Madrid, SpainCorrespondence: María Presa, Pº Joaquín Rodrigo 4- letra I, Pozuelo de Alarcón, Madrid, 28224, Spain, Tel +34 917 157 147, Email mpresa@porib.comPurpose: The objective of the present study was to evaluate the efficiency of lorlatinib compared to alectinib and brigatinib for the treatment of adult patients with anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC) previously not treated, in Spain.Methods: A partitioned survival model comprised progression free, non-intracranial progression, intracranial progression, and death health states was constructed to estimate the total costs, life-years gained (LYG) and quality-adjusted life years (QALYs) accumulated in a lifetime horizon. Overall survival (OS) and progression-free survival (PFS) for lorlatinib were obtained from the CROWN study. For alectinib and brigatinib, a network meta-analysis of randomized controlled trials was conducted to estimate OS and PFS hazard ratios versus crizotinib. Utilities were estimated based on EQ-5D-5L data derived from the CROWN (lorlatinib), ALEX (alectinib) and ALTA-1L (brigatinib) studies. According to the Spanish National Health Service perspective the total costs (expressed in euros using a 2021 cost year) included drug acquisition and the administration’s subsequent treatment, ALK+ advanced NSCLC management and adverse-event management, and palliative care. Unitary costs were obtained from local cost databases and literature. Costs, LYGs and QALYs were discounted at 3% annually. Deterministic and probabilistic sensitivity analyses were used to test the model’s robustness.Results: Lorlatinib provided higher health outcomes (+0.70 LYG/patient, +1.42 QALYs/patient) and lower costs (-€ 9239/patient) than alectinib. Lorlatinib yielded higher LYG (+1.74) and QALYs (+2.30) versus brigatinib but higher costs/patient (+€ 36,627), resulting in an incremental-cost-effectiveness-ratio of € 15,912/QALY gained.Conclusion: The results of this study suggest that lorlatinib may be a dominant treatment option versus alectinib. Considering a willingness-to-pay threshold of € 25,000/QALY, lorlatinib may be an efficient option compared to brigatinib.Keywords: advanced non-small cell lung cancer, lorlatinib, ALK+, cost-effectiveness analysis, cost-utility analysis

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Background: The survival benefits and adverse effects of pembrolizumab 2 mg/kg intravenously (IV) every 3 weeks (Q3W) in advanced non-small lung cancer (NSCLC) are well documented in the literature. Based on pharmacokinetic models, a pembrolizumab 4 mg/kg IV every 6 weeks (Q6W) dosing regimen is also approved in some countries. To date, there is no direct comparison in the literature between these 2 regimens in advanced NSCLC. Methods: This retrospective study included 80 patients with advanced NSCLC who received pembrolizumab monotherapy 4 mg/kg Q6W between March 1, 2020 and December 31, 2021 and 80 patients with advanced NSCLC who received pembrolizumab monotherapy 2 mg/kg Q3W between January 1, 2017 and January 15, 2019 at Institut universitaire de cardiologie et de pneumologie de Québec (IUCPQ). The primary outcomes of this study were to compare overall survival (OS), progression-free survival (PFS) as well as the occurrence and severity of immune-mediated adverse events (AEs) in patients with advanced NSCLC who received pembrolizumab Q6W vs Q3W. Data cutoff date was December 15, 2022. Results: Median follow-up was 14.5 ± 8.6 months in the Q6W group and 18.3 ± 19.6 months in the Q3W group. Median PFS was 6.9 months (CI 95% 5.0-10.7) in the Q6W group vs 8.9 months (CI 95% 5.6-14.1) in the Q3W group (adjusted HR 1.27 (CI 95% 0.85-1.89), P =.25). Median OS was not reached in the Q6W group vs 20.5 months (CI 95% 13.7-29.8) in the Q3W group (adjusted HR 0.80 (CI 95% 0.50-1.29), P =.36). Immune-mediated AEs of grade ≥ 3 occurred in 18% of patients in the Q6W group and in 19% of those in the Q3W group. Conclusions: In this unicentric retrospective study, the pembrolizumab Q6W dosing regimen was comparable to the Q3W in terms of OS, PFS, and toxicity. This study compared overall survival, progression-free survival and immune-related adverse events in patients with advanced non-small cell lung cancer who received pembrolizumab every 6 weeks versus every 3 weeks. [ABSTRACT FROM AUTHOR]

Objective To evaluate predictive factors affecting the short-term efficacy of PD-1 inhibitors in non-small cell lung cancer (NSCLC) and to construct a prediction model. Methods From October 2019 to November 2021, 221 patients with advanced NSCLC who met the inclusion criteria and were treated with PD-1 inhibitors were prospectively enrolled. Patients who were enrolled before May 1st, 2021 were included inthe modeling group (n=149), whereas those who enrolled thereafter were included in the validation group (n=72). The general clinical data of patients, information of the four TCM diagnoses were collected, and TCM syndrome elements were identified. R software version 4.0.4 was used in constructing a nomogram clinical prediction model of objective response rate. The predictive ability and discrimination of the model were evaluated and externally validated by using a validation group. Results After two to four cycles of PD-1 inhibitor therapy in 221 patients, the overall objective response rate was 44.80%. Multivariate logistic regression analysis of the modeling group showed that the TPS score (OR=0.261, P=0.001), number of treatment lines (OR=3.749, P=0.002), treatment mode (OR=2.796, P=0.019), qi deficiency disease syndrome elements (OR=2.296, P=0.043), and syndrome elements of yin deficiency disease (OR=3.228, P=0.005) were the independent predictors of the short-term efficacy of PD-1 inhibitors. Based on the above five independent predictors, a nomogram prediction model for the short-term efficacy of PD-1 inhibitors was constructed. The AUC values of the modeling and validation groups were 0.8317 and 0.7535, respectively. The calibration curves of the two groups showed good agreement between the predicted and true values. The mean absolute errors were 0.053 and 0.039, indicating that the model has good predictive performance. Conclusion The nomogram model constructed on the basis of the syndrome elements of Qi-deficiency disease and Yin-deficiency syndrome of TCM, as well as TPS score, number of treatment lines and treatment mode, is a stable and effective tool for predicting the short-term efficacy of PD-1 inhibitors in advanced non-small cell lung cancer. [ABSTRACT FROM AUTHOR]

Introduction: Docetaxel is an established standard therapy after osimertinib and platinum-based doublet chemotherapy (Pt-doublet) for locally advanced or metastatic non-small cell lung cancer (NSCLC) with an epidermal growth factor receptor gene (EGFR) mutation. To facilitate future therapeutic developments in these patients after treatment with osimertinib and Pt-doublet, we estimated the outcomes of currently used post-treatment therapies. Methods: Data of patients with NSCLC who received at least one medication after osimertinib and Pt-doublet between April 2008 and August 2021 were extracted from the Medical Data Vision claims database. The duration of treatment (DoT) (first treatment after osimertinib and Pt-doublet) and overall survival (OS) were estimated. The index date was the first day on which the medication was prescribed. Results: In total, 731 patients (mean age 64 years) were screened. The most frequent post-treatments were docetaxel-based chemotherapy (30.2%), immune checkpoint inhibitor (ICI) alone or in combination (17.2%), first-/second-generation EGFR-tyrosine kinase inhibitors (16.7%), osimertinib (16.3%), and Pt-doublet (5.2%). The median DoT and OS (95% confidence interval) of all post-treatments were 3.5 (3.27, 3.77) and 10.3 (9.3, 12.1) months, respectively, reflecting the median DoT (3.8 months) and OS (10.0 months) of docetaxel-based chemotherapy. Among all post-treatment regimens, ICIs resulted numerically the shortest [2.77 (2.33, 3.00) months] and osimertinib the longest [4.40 (3.47, 5.67) months] median DoT. The median OS was shortest in patients post-treated with ICIs [7.07 (5.40, 9.90) months] and longest in patients rechallenged with Pt-doublet (12.27 months), followed by patients post-treated with osimertinib (11.70 months). In a subset analysis of patients who received first-line osimertinib and second-line Pt-doublet as well as Pt-doublet immediately after osimertinib, those post-treated with ICIs had the shortest median DoT. Conclusion: Given the limited real-world efficacy on EGFR-mutant NSCLC resistant to osimertinib and platinum-based chemotherapy, the development of more highly potent post-treatment therapies is warranted. [ABSTRACT FROM AUTHOR]

Introduction: Advanced or metastatic non-small cell lung cancer (NSCLC) is associated with significant symptom burden. It is important to understand the impact of these disease-and treatment-related symptoms on patients' daily lives and explore from a patient perspective what constitutes a meaningful change in NSCLC symptoms. Methods: Patient experience of advanced or metastatic NSCLC was explored in this prospective, non-interventional qualitative research study recruiting patients from the United States (US). Interviews were conducted to explore the most important symptoms, daily life impacts, and patients' perspectives of what constitutes meaningful change when considering their current symptoms versus 6-12 months prior, based on the Patient Global Impression of Severity (PGI-S) and Patient Global Impression of Change (PGI-C) items. Results: Between February and April 2022, 19 US-based patients with Stage IV NSCLC were recruited; 95% were female, 63% were White, 79% had been diagnosed >1 year prior, and 63% were receiving targeted therapy. Over half the patients indicated their most important symptoms were fatigue, shortness of breath, and cough. Patient differentiation between whether symptoms were disease- or treatment-related lacked concordance, and often patients were unable to distinguish the two. The most frequently mentioned impacts of these symptoms on patients' daily lives were difficulty walking, sleep disturbance, anxiety/depression, impact on relationships, and difficulty doing daily tasks. Most patients considered a one-point change on the PGI-S or PGI-C to be meaningful based on rating their symptom severity at the time of the interview compared with 6-12 months before the interview. Conclusion: Based on their own symptom experience, patients with advanced or metastatic NSCLC indicated a one-point threshold for meaningful change, whether improvement or worsening. This suggests a one-point change on the PGI-S or PGI-C may be a potential anchor for patient-reported outcome (PRO) endpoints used in clinical trials. It is important to use PRO instruments that capture the symptoms and impacts identified as most important to patients. These findings highlight the importance of using qualitative methods to assess disease-related symptoms, treatment-related side effects, and the impacts on daily life for patients with advanced or metastatic NSCLC, underscoring how qualitative assessments can complement quantitative PRO instruments for evaluating clinical trials. [ABSTRACT FROM AUTHOR]

Ferroptosis is a novel regulatory cell death characterized by iron dependence and mainly caused by the accumulation of lipid peroxides and reactive oxygen species in the cell. This process plays an important role in the development of many malignancies, and has been extensively studied in lung cancer, especially in antitumor therapy. In recent years, the role of ferroptosis in tumor immunotherapy has been gradually explored. Studies showed that targeting ferroptosis can improve the therapeutic efficacy of antitumor immunotherapy. In addition, immunotherapy and ferroptosis can work synergistically to enhance the effectiveness of antitumor therapy, suggesting a potential relationship between ferroptosis and immunotherapy and the possible reversal of immune drug resistance. This study aims to elucidate the characteristics of ferroptosis, and the role and potential clinical applications of ferroptosis in the antitumor immunotherapy of advanced non-small cell lung cancer. We also explore the role of some nanomaterials that target the onset of tumor ferroptosis in facilitating immunotherapy [ABSTRACT FROM AUTHOR]

A large proportion of patients with non-small cell lung cancer (NSCLC) are diagnosed with metastatic and incurable advanced lung cancer at the time of discovery, so these patients are given no surgical opportunity and have a low 5-year survival rate. In the era of immunotherapy, many kinds of immune checkpoint inhibitors (ICIs) have been approved as the first/second-line treatment for patients with advanced NSCLC with negative driving genes and have been combined with radiotherapy as an important treatment strategy for patients with advanced NSCLC. The innovative strategy of combining radiotherapy and immunotherapy has shown feasibility as supported by practical evidence in clinical research. A preclinical experiment of observing the immune mechanism at the molecular and cellular levels preliminarily revealed the interaction among tumor, radiation, and immune system. This paper briefly reviews the progress of combined radiotherapy and immunotherapy in the treatment of advanced NSCLC with negative drvier genes. [ABSTRACT FROM AUTHOR]

Abstract Background Lung cancer is frequently accompanied by interstitial lung disease (ILD), and the overall survival (OS) of patients with these comorbidities is poor. Thus, we developed a nomogram for the prediction of the OS of patients with advanced non‐small cell lung cancer (NSCLC) and ILD. Patients and Methods Patients with wild‐type gene advanced NSCLC with and without ILD who underwent chemotherapy between 2014 and 2019 were enrolled in the present study. The 0.5‐ and 1‐year progression‐free survival (PFS) and overall survival (OS) times of patients with and without ILD were determined using the Kaplan–Meier method. Cox regression was used to assess the prognostic value of clinical factors for patients with ILD. Based on the multivariate regression results, a nomogram for survival prediction was developed. The nomogram was validated using calibration curve. Results Data from 155 patients with lung cancer and ILD and 118 matched patients with lung cancer alone who were receiving first‐line chemotherapy were analyzed. The first‐line chemotherapy regimens were paclitaxel + carboplatin, pemetrexed + carboplatin, gemcitabine + carboplatin, and other. The median PFS and OS were significantly shorter in patients with than in those without ILD (3.0 vs. 7.0 months [p

Abstract Background Patients with epidermal growth factor receptor (EGFR)‐mutated, advanced non–small cell lung cancer have received immunochemotherapy as one of the treatment options after tyrosine kinase inhibitor (TKI) failure. Methods We retrospectively examined EGFR‐mutant patients treated with atezolizumab‐bevacizumab‐carboplatin‐paclitaxel (ABCP) therapy or platinum‐based chemotherapy (Chemo) after EGFR‐TKI therapy at five institutions in Japan. Results A total of 57 patients with EGFR mutation were analyzed. The median progression‐free survival (PFS) and overall survival (OS) in the ABCP (n = 20) and Chemo (n = 37) were 5.6 and 20.9 months, 5.4 and 22.1 months, respectively (PFS, p = 0.39; OS, p = 0.61). In programmed death‐ligand 1 (PD‐L1)–positive patients, median PFS in the ABCP group was longer than in the Chemo group (6.9 vs. 4.7 months, p = 0.89). In PD‐L1–negative patients, median PFS in the ABCP group was significantly shorter than in the Chemo group (4.6 vs. 8.7 months, p = 0.04). There was no difference in median PFS between the ABCP and Chemo groups in the subgroups of brain metastases, EGFR mutation status, or chemotherapy regimens, respectively. Conclusion The effect of ABCP therapy and chemotherapy was comparable in EGFR‐mutant patients in a real‐world setting. The indication for immunochemotherapy should be carefully considered, especially in PD‐L1–negative patients.

Introduction: Data on utilization and clinical outcomes of programmed cell death protein or programmed death-ligand 1 (PD-[L]1) inhibitors in NSCLC with uncommon oncogenic alterations is limited. Methods: This retrospective study used a deidentified U.S. nationwide clinicogenomic database to select patients with advanced nonsquamous NSCLC without EGFR, ALK, or ROS1 alterations, diagnosed from January 1, 2016 to September 30, 2020, who initiated first-line therapy. Our objectives were to summarize characteristics and treatment patterns for patients with four little-studied genomic alterations or driver-negative NSCLC. We estimated Kaplan-Meier real-world time on treatment (rwTOT) and time to next treatment for patients receiving PD-(L)1 inhibitors. The data cutoff was September 30, 2021. Results: Of the 3971 eligible patients, 84 (2%) had NSCLC with BRAF V600E mutation, 117 (3%) had MET exon 14 skipping mutation, 130 (3%) had MET amplification, 91 (2%) had ERBB2 activation mutation, and 691 patients (17%) had driver-negative NSCLC. Patient characteristics differed among cohorts as expected. The most common first-line regimen in each cohort was a PD-(L)1 inhibitor as monotherapy or in combination with chemotherapy. The median rwTOT with anti–PD-(L)1 monotherapy was 4.6 months in the driver-negative cohort and ranged from 2.9 months (ERBB2 mutation) to 7.6 months (BRAF V600E mutation). The median rwTOT with anti–PD-(L)1-chemotherapy combination was 5.2 months in the driver-negative cohort and 6 months in all but the BRAF V600E cohort (17.5 mo). The patterns of real-world time to next treatment results were similar. Conclusions: Substantial use of anti–PD-(L)1 therapy and associated clinical outcomes are consistent with previous real-world findings and suggest no detriment from PD-(L)1 inhibitors for advanced nonsquamous NSCLC harboring one of these four genomic alterations relative to driver-negative NSCLC.

IntroductionAdvanced or metastatic non-small cell lung cancer (NSCLC) is associated with significant symptom burden. It is important to understand the impact of these disease-and treatment-related symptoms on patients’ daily lives and explore from a patient perspective what constitutes a meaningful change in NSCLC symptoms.MethodsPatient experience of advanced or metastatic NSCLC was explored in this prospective, non-interventional qualitative research study recruiting patients from the United States (US). Interviews were conducted to explore the most important symptoms, daily life impacts, and patients’ perspectives of what constitutes meaningful change when considering their current symptoms versus 6–12 months prior, based on the Patient Global Impression of Severity (PGI-S) and Patient Global Impression of Change (PGI-C) items.ResultsBetween February and April 2022, 19 US-based patients with Stage IV NSCLC were recruited; 95% were female, 63% were White, 79% had been diagnosed >1 year prior, and 63% were receiving targeted therapy. Over half the patients indicated their most important symptoms were fatigue, shortness of breath, and cough. Patient differentiation between whether symptoms were disease- or treatment-related lacked concordance, and often patients were unable to distinguish the two. The most frequently mentioned impacts of these symptoms on patients’ daily lives were difficulty walking, sleep disturbance, anxiety/depression, impact on relationships, and difficulty doing daily tasks. Most patients considered a one-point change on the PGI-S or PGI-C to be meaningful based on rating their symptom severity at the time of the interview compared with 6–12 months before the interview.ConclusionBased on their own symptom experience, patients with advanced or metastatic NSCLC indicated a one-point threshold for meaningful change, whether improvement or worsening. This suggests a one-point change on the PGI-S or PGI-C may be a potential anchor for patient-reported outcome (PRO) endpoints used in clinical trials. It is important to use PRO instruments that capture the symptoms and impacts identified as most important to patients. These findings highlight the importance of using qualitative methods to assess disease-related symptoms, treatment-related side effects, and the impacts on daily life for patients with advanced or metastatic NSCLC, underscoring how qualitative assessments can complement quantitative PRO instruments for evaluating clinical trials.

Background: Previous studies revealed that Programmed cell death protein 1 (PD-1)/Programmed cell death-Ligand protein 1 (PD-L1) inhibitors plus anti-angiogenic agents had extensive anti-tumor activities. However, almost all studies on the efficacy and safety of PD-1/PD-L1 inhibitors plus anti-angiogenic agents as second or later-line treatment for patients with advanced non-small cell lung cancer are non-randomized controlled trials with small sample sizes, which might lead to a lack of effective metrics to assess the effectiveness and safety of the therapeutic regimen. Here, thismeta-analysis aimed to evaluate the efficacy and safety of PD-1/PD-L1 inhibitors plus anti-angiogenic agents as second or later-line treatment for patients with advanced non-small cell lung cancer. Methods: A single-arm meta-analysis was performed, and published literature from PubMed, Web of Science and Embase databases as of January 13, 2023, was systematically retrieved. We used the Cochrane risk of bias tool and methodological index for non-randomized studies (MINORS) Methodological items to evaluate the quality of eligible clinical trials. Outcomes including overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were extracted for further analysis. The random effect model is used to calculate the pooled parameters. Results: 19 studies (16 were non-comparative single-arm clinical trials and 3 were randomized controlled trials) were enrolled in this meta-analysis. In terms of tumor response, the pooled ORR and DCR were 22.4% (95% CI, 16.6-28.1%) and 76.8% (95% CI, 72.6-81.1%), respectively. With regard to survival analysis, the pooled PFS and OS were 5.20 (95% CI, 4.46-5.93) months and 14.09 (95% CI, 13.20-14.97) months, respectively. The pooled grade ≥3 adverse effect (AE) rate was 47.6% (95% CI, 33.1-62.0%). Conclusion: PD-1/PD-L1 inhibitors plus anti-angiogenic agents has promising efficacy and safety as second or later-line treatment in patients with advanced non-small cell lung cancer. [ABSTRACT FROM AUTHOR]

Background: The EMPOWER-LUNG 3 clinical trial has shown that cemiplimab plus chemotherapy (CCT) significantly extended overall survival (OS) and progression-free survival (PFS) for patients with advanced non-small cell cancer (NSCLC) compared to placebo plus chemotherapy (PCT). However, the cost-effectiveness of this new treatment option remains unknown. Thus, we evaluated the cost-effectiveness of CCT versus (vs.) PCT as the first-line treatment for patients with advanced NSCLC from the perspective of the Chinese healthcare system. Methods: We constructed a Markov model to evaluate the cost-effectiveness of CCT as the first-line treatment for patients with advanced NSCLC. The transition probabilities were extracted from the survival data of the EMPOWER-LUNG 3 trial. The drugs' costs were referred from national tender prices, while other model input parameters were derived from the EMPOWER-LUNG 3 trial and published literature. The outcome parameters mainly included quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs). One-way sensitivity analysis and probabilistic sensitivity analysis were performed to evaluate the robustness of the model outcomes. Results: Compared to PCT, in the CCT regimen, an additional $79,667 was spent in terms of the total cost and with an additional 0.31 QALYs, resulting in an ICER value of $253,148/QALY. Sensitivity analysis indicated that the hazard ratio (HR) of OS, the cost of cemiplimab (100 mg), and the HR of PFS, all significantly impacted the model's results. The probability of CCT (vs. PCT) being cost-effective was 0% at a willingness-to-pay threshold of $38,201/QALYs in China. The scenario analysis showed that when the price of cemiplimab was reduced to less than $184.09/100 mg, the CCT regimen could be considered cost-effective as the first-line treatment for patients with advanced NSCLC compared to the PCT. Conclusion: In China, the CCT was not cost-effective as the first-line treatment for patients with advanced NSCLC. [ABSTRACT FROM AUTHOR]

Background: EMPOWER‐Lung 3, a randomized 2:1 phase 3 trial, showed clinically meaningful and statistically significant overall survival improvement with cemiplimab plus platinum‐doublet chemotherapy versus placebo plus chemotherapy for first‐line treatment of advanced non–small cell lung cancer. This study evaluated patient‐reported outcomes (PROs). Methods: PROs were assessed at day 1 (baseline), the start of each treatment cycle (every 3 weeks) for the first six doses, and then at start of every three cycles, using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life‐Core 30 (QLQ‐C30) and Quality of Life‐Lung Cancer Module (QLQ‐LC13) questionnaires. Prespecified analyses included a longitudinal mixed‐effect model comparing treatment arms and a time to definitive clinically meaningful deterioration (TTD) analysis performed for global health status/quality of life (GHS/QoL) and all scales from the questionnaires. Between‐arm TTD comparisons were made using a stratified log‐rank test and proportional hazards model. Results: A total of 312 patients were assigned to receive cemiplimab plus platinum‐doublet chemotherapy and 154 to receive placebo plus chemotherapy; 391 (83.9%) were male and the median age was 63.0 years (range, 25–84). For pain symptoms (EORTC QLQ‐C30), a statistically significant overall improvement from baseline (−4.98, 95% confidence interval [CI] −8.36 to −1.60, p =.004) and a statistically significant delay in TTD (hazard ratio, 0.39; 95% CI, 0.26–0.60, p <.0001) favoring cemiplimab plus chemotherapy were observed. Statistically significant delays in TTD, all favoring cemiplimab plus chemotherapy, were also observed in functioning and symptom scales. A significant overall improvement from baseline in GHS/QoL was seen for cemiplimab plus chemotherapy compared with nonsignificant overall change from baseline for placebo plus chemotherapy (1.69, 95% CI, 0.20–3.19 vs. 1.08, 95% CI, –1.34 to 3.51; between arms, p =.673). No analyses yielded statistically significant PRO results favoring placebo plus chemotherapy for any QLQ‐C30 or QLQ‐LC13 scale. Conclusion: Cemiplimab plus chemotherapy resulted in significant overall improvement in pain symptoms and delayed TTD in cancer‐related and lung cancer–specific symptoms and functions. Cemiplimab plus chemotherapy significantly improves pain in advanced lung cancer patients; significant delay in other symptom and function deterioration is also achieved. These results further support positive benefit‐risk profile of cemiplimab plus chemotherapy. [ABSTRACT FROM AUTHOR]

Purpose: This study was conducted to estimate the indirect cost of locally advanced and metastatic non-small cell lung cancer (NSCLC) without sensitizing EGFR and ALK alterations in China and explore the predictors from both patient and caregiver perspectives. Methods: Data were obtained from a nationwide cross-sectional study for the patients with advanced NSCLC (stage IIIB–IV) and their caregivers. Indirect medical cost was estimated as health productivity loss based on self-reported income and loss of work time. The generalized linear model was used to assess the independent associations between statistically significant variables and indirect economic burden. Results: 611 pairs of patients and patient caregivers from 13 medical centers in five provinces in China participated in this investigation. The indirect medical cost associated with advanced NSCLC since the patient diagnosed was $1413 per capita in China. General linear regression results showed that the indirect medical cost was significantly influenced by duration of disease since diagnosis, treatment options, caregivers' occupation and age (P < 0.05). Conclusion: The indirect economic burden linked to advanced NSCLC in China is considerable on patients, and their caregivers. To minimize the severe challenges of indirect economic burden related to advanced NSCLC, expanding the coverage of the medical insurance and assistance system to reimburse part of the indirect costs related to cancer, as well as strengthening the accessibility for more effective therapies to improve the prognosis of advanced NSCLC, and further promote the patients and their caregivers to return to work or normal life may be the potentially feasible approaches. [ABSTRACT FROM AUTHOR]

Objective: To explore the effect of targeted therapy combined with interventional therapy on the efficacy and long-term recurrence rate of advanced non-small cell lung cancer. Methods: 220 patients with advanced non-small cell lung cancer admitted to our hospital from January 2017 to December 2019 were selected as the study subjects for retrospective analysis. According to the different treatment methods selected by the patients, 110 patients who chose simple PP regimen chemotherapy were divided into matched group, and 110 patients who chose targeted therapy combined with 125I radioactive particle implantation on the basis of PP regimen chemotherapy were divided into observation group, The survival of the two groups, the levels of angiogenic factors and tumor markers before and after treatment for 3 months, the 1-year, 2-year and 3-year recurrence rates and adverse reactions were compared. Results: The median PFS of the observation group was 11.26 (2.38-24.13), and the median PFS of the matched group was 9.25 (2.24-17.22). The observation group was higher than the matched group(x² =4.536, P=0.041), as shown in Figure 1A. The median OS of the observation group was 21.23 (4.84~62.73), and the median OS of the matched group was 16.52 (5.27~50.27). The observation group was higher than the matched group, and the difference was statistically significant（x² =5.262, P=0.022); There was no difference in the levels of basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), angiogenesis factor, human cytokeratin 21-1 fragment (Cyfra21-1) and carbohydrate antigen 125(CA125) tumor markers between the two groups before treatment (P>0.05), After treatment, the levels of bFGF, VEGF angiogenesis factor, CA125 and Cyfra21-1 tumor markers in the two groups were lower than those in the matched group (P<0.05); The long-term total recurrence rate of patients in the observation group was lower than that in the matched group (P<0. 05); There was no difference in the adverse reactions of 0~II and III~IV between the two groups (P>0.05). Conclusion: Targeted therapy combined with 125I radioactive particle implantation can improve the survival and progression-free survival of patients with advanced non-small cell lung cancer on the basis of conventional chemotherapy, improve the level of inflammatory markers in patients, reduce the long-term recurrence rate, and have high safety, which is worthy of clinical promotion. [ABSTRACT FROM AUTHOR]

Introduction: Treatment landscape for advanced/metastatic NSCLC (aNSCLC) has evolved considerably over the past few decades with the advent of targeted therapies for epidermal growth factor receptor-mutated (EGFRm+) aNSCLC treatment. This study described real-world patient and disease characteristics, treatment and practice patterns, and clinical, economic, and patient-reported outcomes (PROs) in patients with EGFRm+ aNSCLC. Methods: Data were derived from the Adelphi NSCLC Disease Specific Programme™ (DSP™), a point-in-time survey conducted between July and December 2020. The survey included oncologists and pulmonologists, and their consulting patients (with physician-confirmed EGFRm+ aNSCLC) from nine countries: the US, Brazil, the UK, Italy, France, Spain, Germany, Japan, and Taiwan. All analyses were descriptive. Results: Overall, 542 physicians reported data for 2857 patients (mean age 65.6 years), and most patients were female (56.0%), white (61.0%), and had stage IV disease at initial diagnosis (76.0%), and adenocarcinoma histology (89.0%). Most patients received EGFR-tyrosine kinase inhibitors (TKI) therapy in first- (91.0%), second- (74.0%), and third-line (67.0%). The most common tumor samples and methods for EGFR detection were EGFR-specific mutation detection tests (44.0%) and core needle biopsy (56.0%). Median time to next treatment was 14.0 (IQR 8.0–22.0) months and disease progression was the main physician-reported reason for early discontinuation. The most common physician-reported disease symptoms were cough (51.0%), fatigue (37.0%), and dyspnea (33.0%). In patients assessed for PROs, mean EQ-5D-5L index and FACT-L health utility scores were 0.71 and 83.5, respectively. On average, patients lost 10.6 h of work/week for approximately 29.2 weeks due to EGFRm+ aNSCLC. Conclusion: This real-world multinational data set showed that most patients with EGFRm+ aNSCLC were treated per the country relevant clinical guidelines, with progression as the main reason for early treatment discontinuation. For the included countries, these findings may offer a useful benchmark for decision makers to determine future allocation of healthcare resources for patients with EGFRm+ aNSCLC. [ABSTRACT FROM AUTHOR]

C-ros oncogene 1 (ROS1) fusion is a pathogenic driver gene in non-small cell lung cancer (NSCLC). Currently, clinical guidelines from the National Comprehensive Cancer Network (NCCN) have recommended molecular pathologic tests for patients with NSCLC, including the detection of the ROS1 gene. Crizotinib is a small molecule tyrosine kinase inhibitor of anaplastic lymphoma kinase (ALK), ROS1, and mesenchymal-epithelial transition (MET). In recent years, the efficacy of crizotinib in NSCLC patients with ROS1 fusion has been reported. Here, a 77-year-old woman was diagnosed with stage IVA lung adenocarcinoma harboring a novel low-density lipoprotein receptor (LDLR)- ROS1 fusion variant. This novel LDLR-ROS1 fusion was identified by targeted DNA next-generation sequencing (NGS) panel and then verified by RNA fusion panel based on amplicon sequencing. This patient benefited from subsequent crizotinib therapy and achieved progression-free survival of 15 months without significant toxic symptoms. Our case report recommended a promising targeted therapeutic option for patients with metastatic NSCLC with LDLR-ROS1 fusion and highlighted the importance of genetic testing for accurate treatment. [ABSTRACT FROM AUTHOR]

Background: Patients with epidermal growth factor receptor (EGFR)‐mutated, advanced non–small cell lung cancer have received immunochemotherapy as one of the treatment options after tyrosine kinase inhibitor (TKI) failure. Methods: We retrospectively examined EGFR‐mutant patients treated with atezolizumab‐bevacizumab‐carboplatin‐paclitaxel (ABCP) therapy or platinum‐based chemotherapy (Chemo) after EGFR‐TKI therapy at five institutions in Japan. Results: A total of 57 patients with EGFR mutation were analyzed. The median progression‐free survival (PFS) and overall survival (OS) in the ABCP (n = 20) and Chemo (n = 37) were 5.6 and 20.9 months, 5.4 and 22.1 months, respectively (PFS, p = 0.39; OS, p = 0.61). In programmed death‐ligand 1 (PD‐L1)–positive patients, median PFS in the ABCP group was longer than in the Chemo group (6.9 vs. 4.7 months, p = 0.89). In PD‐L1–negative patients, median PFS in the ABCP group was significantly shorter than in the Chemo group (4.6 vs. 8.7 months, p = 0.04). There was no difference in median PFS between the ABCP and Chemo groups in the subgroups of brain metastases, EGFR mutation status, or chemotherapy regimens, respectively. Conclusion: The effect of ABCP therapy and chemotherapy was comparable in EGFR‐mutant patients in a real‐world setting. The indication for immunochemotherapy should be carefully considered, especially in PD‐L1–negative patients. [ABSTRACT FROM AUTHOR]

Background: Previous studies have shown that the predictive value of traditional linear (time domain and frequency domain) heart rate variability (HRV) for the survival of patients with advanced non-small cell lung cancer (NSCLC) is controversial. Nonlinear methods, based on the concept of complexity, have been used to evaluate HRV, providing a new means to reveal the physiological and pathological changes in HRV. This study aimed to assess the association between heartbeat complexity and overall survival in patients with advanced NSCLC. Methods: This study included 78 patients with advanced NSCLC (mean age: 62.0 ± 9.3 years). A 5-min resting electrocardiogram of advanced NSCLC patients was collected to analyze the following HRV parameters: time domain indicators, i.e., standard deviation of the normal-normal intervals (SDNN) and root mean square of successive interval differences (RMSSD); frequency domain indicators, i.e., total power (TP), low frequency power (LF), high frequency power (HF), and the ratio of LF to HF (LF/HF); nonlinear HRV indicators characterizing heartbeat complexity, i.e., approximate entropy (ApEn), sample entropy (SampEn), and recurrence quantification analysis (RQA) indexes: mean diagonal line length (Lmean), maximal diagonal line length (Lmax), recurrence rate (REC), determinism (DET), and shannon entropy (ShanEn). Results: Univariate analysis revealed that the linear frequency domain parameter HF and nonlinear RQA parameters Lmax, REC, and DET were significantly correlated with the survival of advanced NSCLC patients (all p < 0.05). After adjusting for confounders in the multivariate analysis, HF, REC, and DET were found to be independent prognostic factors for the survival of patients with advanced NSCLC (all p < 0.05). Conclusion: There was an independent association between heartbeat complexity and survival in advanced NSCLC patients. The nonlinear analysis method based on RQA may provide valuable additional information for the prognostic stratification of patients with advanced NSCLC and may supplement the traditional time domain and frequency domain analysis methods. [ABSTRACT FROM AUTHOR]

• Whether PK-guided pembrolizumab in advanced NSCLC is a rational therapeutic strategy. • Pembrolizumab administration under PK-guided was an alternative rational strategy. • Personalized optimal treatment of pembrolizumab can reduce economic toxicity. Pembrolizumab is recommended with a fixed dose of 200 mg 3-weekly. We performed this study to explore the clinical efficacy and safety of pharmacokinetic (PK)-guided pembrolizumab administration in advanced non-small cell lung cancer (NSCLC). In this prospective exploratory study, we enrolled advanced NSCLC patients in Sun Yat-Sen University Cancer Center. Eligible patients received pembrolizumab 200 mg 3-weekly with or without chemotherapy for four cycles, then for patients without progressive disease (PD), pembrolizumab was administrated in new dose-intervals according to steady state plasma-concentration (Css) of pembrolizumab until PD. We set the effective concentration (Ce) at 15 μg/ml and new dose-intervals (T) was calculated according to Css of pembrolizumab using following equation: Css × 21D = Ce (15 μg/ml) × T. Primary endpoint was the progression-free survival (PFS), secondary endpoints were objective response rate (ORR) and safety. Besides, advanced NSCLC patients received pembrolizumab 200 mg 3-weekly and more than four cycles in our center were defined as the history-controlled cohort. Patients with Css of pembrolizumab underwent genetic polymorphism analysis of variable number of tandem repeats (VNTR) region in neonatal Fc receptor (FcRn). The study was registered at ClinicalTrials.gov, NCT05226728. A total 33 patients received pembrolizumab in new adjusted dose-intervals. The Css of pembrolizumab ranged from 11.01 to 61.21 μg/ml, 30 patients need prolonged intervals (22-80d) and 3 shortened intervals (15–20 d). In PK-guided cohort, the median PFS was 15.1 months and ORR 57.6 %, whereas in history-controlled cohort was 7.7 months and ORR 48.2 %. The immune-related adverse events were 15.2 % and 17.9 % between two cohort. The VNTR3/VNTR3 genotype of FcRn had significantly higher Css of pembrolizumab than VNTR2/VNTR3 (p = 0.005). PK-guided pembrolizumab administration showed promising clinical efficacy and manageable toxicity. Meanwhile less frequent dosing of pembrolizumab by PK-guided could reduce financial toxicity potentially. This provided an alternative rational therapeutic strategy of pembrolizumab in advanced NSCLC. [ABSTRACT FROM AUTHOR]

Summary: The objective of this study was to evaluate the safety and tolerability of DS-1205c, an oral AXL-receptor inhibitor, in combination with osimertinib in metastatic or unresectable EFGR-mutant non-small cell lung cancer (NSCLC) patients who developed disease progression during EGFR tyrosine kinase inhibitor (TKI) treatment. An open-label, non-randomized phase 1 study was conducted in Taiwan, in which 13 patients received DS-1205c monotherapy at a dosage of 200, 400, 800, or 1200 mg twice daily for 7 days, followed by combination treatment with DS-1205c (same doses) plus osimertinib 80 mg once daily in 21-day cycles. Treatment continued until disease progression or other discontinuation criteria were met. At least one treatment-emergent adverse event (TEAE) was reported in all 13 patients treated with DS-1205c plus osimertinib; with ≥ 1 grade 3 TEAE in 6 patients (one of whom also had a grade 4 increased lipase level), and 6 patients having ≥ 1 serious TEAE. Eight patients experienced ≥ 1 treatment-related AE (TRAE). The most common (2 cases each) were anemia, diarrhea, fatigue, increased AST, increased ALT, increased blood creatinine phosphokinase, and increased lipase. All TRAEs were non-serious, with the exception of an overdose of osimertinib in 1 patient. No deaths were reported. Two-thirds of patients achieved stable disease (one-third for > 100 days), but none achieved a complete or partial response. No association between AXL positivity in tumor tissue and clinical efficacy was observed. DS-1205c was well-tolerated with no new safety signals in patients with advanced EGFR-mutant NSCLC when administered in combination with the EFGR TKI osimertinib. ClinicalTrials.gov; NCT03255083. [ABSTRACT FROM AUTHOR]