Advanced Non-small Cell Lung Cancer Research Articles

[Artículo traducido] Adherencia al tratamiento con quimioterapia oral en pacientes con cáncer de pulmón no microcítico localmente avanzado o metastásico: protocolo para un estudio de vida real realizado en farmacia hospitalaria

ObjectiveThis article describes a study protocol for evaluating adherence to oral chemotherapy (OCT) in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) in Spain. MethodsThis multicenter, observational, prospective study will be conducted by six hospital pharmacists from six Spanish hospitals. The study will include men and women aged 18 years or older with a diagnosis of locally advanced or metastatic NSCLC who are being treated or have been prescribed OCT. Once included, the patient will be active and prospectively followed up for 3 months, including four study visits to record information on sociodemographic variables, antineoplastic treatment and adherence, pharmaceutical care, clinical variables, and patient-reported outcomes (PRO) (the 3-level version of EQ-5D, the EORTC Core Quality of Life Questionnaire, the Brief Illness Perception Questionnaire, the Treatment Satisfaction with Medicines Questionnaire, and the PRO version of Common Terminology Criteria for Adverse Events). Twelve months after patient inclusion, we will record information on the disease progression status and dispensed prescriptions. The primary outcome is the percentage of treatment adherence that will be calculated based on the pill count as follows: the difference between the number of pills dispensed minus the number of unused pills will be divided by the number of days of treatment multiplied by the number of pills/day prescribed by the oncologist; this quotient will be multiplied by 100 to obtain the percentage of adherence. Based on the that pill count reconciliation, those with a percentage adherence greater than80% will be primarily categorized as adherent. Secondarily, treatment adherence will be also calculated based on the proportion of days covered and the 4-items Morisky Green Levine Medication Adherence Scale. To analyze the impact of patients' and treatment characteristics on adherence, bivariate analyses will be performed using different adherence cut-off points. To evaluate the impact of adherence on treatment efficacy as evaluated by progression-free survival, we will be using the Kaplan–Meier method and compare it with the log-rank test and univariate Cox regression analysis. ConclusionsWe expect that our study will provide initial information on key aspects of adherence to OCT (measurement, facilitators, and barriers) and its relationship with patients' and clinically relevant outcomes in the setting of NSCLC, and that this information will help in designing pharmaceutical interventions to improve adherence.

Seasonal influences on the efficacy of anti-programmed cell death (ligand) 1 inhibitors in lung cancer.

Seasonal variations in systemic immunity have been reported. This study aimed to evaluate whether seasonality affects the efficacy of anticancer immunotherapy. A total of 604 patients with lung cancer receiving single anti-programmed cell death (ligand) 1 (anti-PD-[L]1) inhibitors from two prospective observational cohorts were screened. Primary outcomes were progression-free survival (PFS) and overall survival (OS). Patients were classified into two groups according to the season when the treatment started: winter (November-February) and other seasons (March-October). Kaplan-Meier analysis and Cox proportional hazards models were fitted to evaluate the impact of seasonality on survival. For validation, propensity score matching was performed. A total of 484 patients with advanced non-small cell lung cancer were included. In an unmatched population, multivariable analysis demonstrated that the winter group (n=173) had a significantly lower risk of progression or death from immunotherapy than the other group (n=311) (PFS: hazard ratio [HR],0.77 [95% confidence interval (CI), 0.62-0.96]; p=.018; OS: HR,0.77 [95% CI, 0.1-0.98]; p=.032). In a propensity score-matched population, the winter group (n=162) showed significantly longer median PFS (2.8 months [95% CI, 1.9-4.1 months] vs. 2.0 months [95% CI, 1.4-2.7 months]; p=.009) than the other group (n=162). The winter group's median OS was also significantly longer than that of the other group (13.4 months [95% CI, 10.2-18.0 months] vs. 8.0 months [95% CI, 3.6-8.7 months]; p=.012). The trend toward longer survival in the winter group continued in subgroup analyses. Starting an anti-PD-(L)1 inhibitor in winter was associated with better treatment outcomes in patients with lung cancer compared to other seasons.

Efficacy of subsequent treatment for unresectable locally-advanced non-small cell lung cancer after relapse of concurrent chemoradiotherapy with durvalumab consolidation therapy: a single-center retrospective study

ObjectivesThe current standard treatment for locally advanced non-small cell lung cancer (LA-NSCLC) is concurrent chemoradiation therapy (CCRT) followed by durvalumab consolidation therapy. Although the trial revealed the survival benefit of adding an immune checkpoint inhibitor (ICI) to the population, the optimal treatment strategy and efficacy of subsequent treatment after relapse remain unclear. Materials and MethodsWe retrospectively collected data from patients with unresectable LA-NSCLC who completed platinum-based CCRT as first-line treatment. Patients who received molecular-targeted therapy for driver gene alterations or did not receive durvalumab as consolidation therapy following the approval were excluded. We assessed differences in regimen and efficacy of subsequent treatment in patients who underwent durvalumab consolidation therapy (D group) and those who did not (CR group). ResultsAmong the 62 eligible patients, 32 were assigned to the D group and 30 to the CR group. Patients in the CR group were more frequently treated with an immune checkpoint inhibitor (ICI)-containing regimen than those in the D group (57% vs. 13%, p < 0.001). The median overall survival from initiation of subsequent treatment was shorter in the D group than in the CR group (13.0 months vs. 26.7 months, hazard ratio 2.60; 95% confidence interval: 1.28–2.56, p=0.008). ConclusionsPatients with unresectable LA-NSCLC who relapsed after durvalumab consolidation therapy received an ICI-containing regimen less frequently, and the efficacy of the subsequent treatment was limited.

Patient-Initiated Nationwide Survey on Testing for Actionable Oncogenic Drivers in Non-Small Cell Lung Cancer in Japan.

Previous reports indicated still low implementation rates of multigene testing for advanced non-small cell lung cancer (NSCLC) in Japan. This is a retrospective study launched at the initiative of lung cancer patients. Patients with stage IV NSCLC from January 2019 to December 2022 were investigated for testing of 8 actionable oncogenic drivers with targeted therapies available as of 2022. A total of 15,719 patients were included. Between 2019 and 2022, the percentage of patients who were not tested for any actionable oncogenic drivers remained the same, ranging from 21.5% to 33.1%. However, since late 2021, the percentage of patients tested for five or more actionable oncogenic drivers has increased. Across hospital categories and regions, the number of actionable oncogenic drivers tested was similar. This patient-initiated national survey in Japan reveals the recent nationwide increase in testing rates for actionable oncogenic drivers in Advanced NSCLC.

Changing Treatment and Metastatic Disease Patterns in Patients with EGFR Mutated Non-Small Cell Lung Cancer: An ATOMIC Registry Analysis

IntroductionOsimertinib is now a standard 1L therapy for EGFR-mutated advanced non-small cell lung cancer (NSCLC). We aimed to characterize patterns of therapy and longitudinal risk of brain and liver metastasis in a cohort of EGFRm NSCLC. MethodsPatients with metastatic EGFRm NSCLC who received 1L systemic therapy at sites within the Academic Thoracic Medical Investigator’s Consortium (ATOMIC) were included; demographic and clinical data including treatment patterns were described. Analyses of overall survival (OS), time to next treatment (TTNT), and incident brain and liver metastasis were performed on patients who started 1L therapy in ≥2015 using Kaplan-Meier method, Cox regression, and cumulative incidence functions. ResultsThe full cohort included 1,132 patients; mean age 63.4 years, 53% White, 68% female, 67% nonsmoker; 830 patients received 1L systemic therapy in ≥2015. The predominant first EGFR-TKI was erlotinib (65%) prior to 2018 and osimertinib (81%) after 2018. The median TTNT after start of 1L therapy was 13.9 months overall, and longest in patients receiving 1L osimertinib (28 months). In the post 2015 cohort, the baseline prevalence of brain metastasis (BM) was 54% and among patients without baseline brain metastasis, the probability of incident BM at 12, 24, and 48 months was 8%, 22% and 44%, respectively. Development of an on-treatment brain metastasis among patients without baseline brain metastasis was associated with a 3.2 times higher risk of death. ConclusionEven in a contemporary era with prevalent osimertinib use, baseline and longitudinal risk of BM development was high. The ongoing risk of developing BM, together with the associated survival detriment, argues for routine surveillance brain MRIs for patients with EGFRm NSCLC, which are not currently included in guidelines.

Comprehensive serum biomarker analysis reveals IL-8 changes as the only predictor of the effectiveness of immune checkpoint inhibitors for patients with advanced non-small cell lung cancer

ObjectivesProgrammed cell death ligand 1 (PD-L1) expression is widely used to predict the effectiveness of PD-(L)1 inhibitors despite its imperfection. Previous studies suggested the utilization of various serum biomarkers; nonetheless, findings are inconclusive because of limited sample sizes or the focus on a single biomarker in many of these studies. This study analyzed multiplex serum biomarkers to explore their predictive ability in a large cohort of patients with advanced non-small-cell lung cancer (NSCLC) treated with a PD-L1 inhibitor in a real-world setting. Materials and MethodsThis was a sub-study of J-TAIL, a prospective observational study of atezolizumab monotherapy in pre-treated patients with advanced NSCLC. From April to October 2019, 262 patients were enrolled from 73 sites in Japan. Serum samples were collected at baseline and at the second dose of atezolizumab. Quantification of the 51 serum cytokines, chemokines, growth factors, and vascular endothelial growth factors was performed using the Luminex platform. Baseline values and fold changes of the time of the second dose to the baseline were examined in association with the effectiveness of atezolizumab. ResultsAmong the 51 proteins assessed, a higher baseline interleukin (IL)-12 level, a higher soluble CD40 ligand fold change, a lower IL-8 fold change were associated with higher objective response rate (ORR). Of these, only the lower IL-8 fold change was associated with better progression-free survival (PFS) (adjusted hazard ratio, 1.98; 95 % confidence interval, 1.45–2.70; P < 0.01). Multivariate analysis demonstrated that the lower IL-8 fold change was an independent factor for both the ORR and PFS. The IL-8 fold change was independent of the neutrophil/lymphocyte ratio, and durable PFS was observed in patients with both low. ConclusionComprehensive serum biomarker analysis revealed that a lower fold change in serum IL-8 was associated with better outcomes in pre-treated patients with advanced NSCLC receiving atezolizumab.

Comment on: Efficacy and safety of crizotinib in the treatment of advanced non-small cell lung cancer with ROS1 gene fusion: A systematic literature review and meta-analysis of real-world evidence

Comment on: Efficacy and safety of crizotinib in the treatment of advanced non-small cell lung cancer with ROS1 gene fusion: A systematic literature review and meta-analysis of real-world evidence

Efficacy of Atezolizumab in Subsequent Lines of Therapy for NSCLC Patients: Insights from Real-World Data.

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. 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). 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.

Correlation of safety and efficacy of atezolizumab therapy across indications

BackgroundThe association between safety and efficacy of immune checkpoint inhibitors is known, but the correlation between severity and impact of specific organ involvement by immune-related adverse events (irAE) and cancer...

Entrectinib versus crizotinib in Asian patients with ROS1-positive non-small cell lung cancer: A matching-adjusted indirect comparison

ObjectivesEntrectinib and crizotinib are the only ROS proto-oncogene 1 receptor (ROS1) tyrosine kinase inhibitors available for most Asian patients. Their efficacy has neither been compared directly in clinical trials in patients with ROS1-positive non-small cell lung cancer (NSCLC), nor indirectly in Asian populations. Thus, we aimed to provide comparative evidence of the efficacy and safety of entrectinib and crizotinib for Asian patients with advanced or metastatic ROS1-positive NSCLC. Materials and MethodsEfficacy, including overall survival (OS) and progression-free survival (PFS), and safety were evaluated using an unanchored matching-adjusted indirect comparison (MAIC). Individual patient data (IPD) from entrectinib trials (ALKA-372–001/EudraCT 2012–000148-88, STARTRK-1/NCT02097810, and STARTRK-2/NCT02568267; dosage, ≥600 mg once daily; enrollment cutoff, 02 July 2020; data cutoff, 02 August 2021) and aggregate data with simulated pseudo-IPD from a crizotinib trial (OxOnc/NCT01945021; dosage, 250 mg twice daily) were analyzed. Key eligibility criteria from the crizotinib trial were applied to IPD from the entrectinib trials. Baseline characteristics were match-adjusted between arms using propensity score weighting. ResultsFifty-two and 127 patients from the entrectinib and crizotinib trials, respectively, were available for evaluation. Median OS was not reached (NR; weighted; 95 % confidence interval [CI] 28.3–NR) in the entrectinib arm and 44.2 months (95 % CI 32.0–NR) in the crizotinib arm (hazard ratio [HR], 0.662; 95 % CI 0.32–1.37). The respective median PFS was 39.4 months (weighted; 95 % CI 10.4–46.8) and 15.9 months (95 % CI 12.9–24.0) (HR, 0.688; 95 % CI 0.37–1.27). Most AEs were Grade 1–2; both drugs were generally well tolerated. Neutropenia was the most common Grade 3 or 4 treatment-related adverse event for both entrectinib and crizotinib. ConclusionsThe outcomes in this MAIC study including Asian patients with ROS1-positive NSCLC showed a trend for greater clinical benefit with entrectinib versus crizotinib. These findings may contribute to better-informed treatment decisions.

Afatinib and Necitumumab in EGFR-Mutant Non-Small Cell Lung Cancer with Acquired Resistance to EGFR Tyrosine Kinase Inhibitors

IntroductionAlthough tyrosine kinase inhibitors (TKIs) are effective against non-small cell lung cancer (NSCLC) harboring sensitizing epidermal growth factor receptor (EGFR) gene mutations, acquired resistance is inevitable. Preclinical studies suggest combining EGFR TKI and monoclonal antibody therapies may have activity in EGFR-mutated NSCLC that has progressed on TKI therapy alone. Therefore, we prospectively evaluated afatinib plus necitumumab in patients with EGFR-mutated NSCLC. MethodsThis was a phase I dose-escalation, dose-expansion trial assessing the safety and efficacy of afatinib plus necitumumab. Patients had advanced or metastatic EGFR-mutated NSCLC with progression after: (1) first-generation TKI if T790M-negative; (2) subsequent line third-generation TKI if T790M-positive; or (3) third-generation TKI in the first-line setting. Dose-escalation followed a 3+3 design. The primary endpoint of dose-expansion was objective response rate (ORR). ResultsA total of 22 patients with EGFR-mutated NSCLC were enrolled. The maximum tolerated dose (MTD) was afatinib 40 mg oral daily plus necitumumab 600 mg intravenous on days 1 and 15 every 28 days. There were no Grade 4-5 adverse events observed, and seven patients (32%) experienced Grade 3 treatment-related adverse events (3 rash; 1 each oral mucositis, diarrhea, headache, and ventricular arrhythmia and tachycardia). In the entire cohort, there were no responses observed, the median progression-free survival (PFS) was 1.8 months, and the disease control rate (DCR) was 36% but varied between subgroups. ConclusionsAfatinib plus necitumumab was safe but showed limited activity in patients with EGFR-mutated NSCLC. Biomarker studies may identify patient subgroups that are more likely to benefit.

A subset of neutrophils activates anti-tumor immunity and inhibits non-small-cell lung cancer progression.

Neutrophils in the tumor microenvironment (TME) are heterogeneous populations associated with cancer prognosis and immunotherapy. However, the plasticity and function of heterogeneous neutrophils in the TME of non-small-cell lung cancer (NSCLC) remain unclear. Here, we show that neutrophils produce high levels of interleukin (IL)-8, which induce the differentiation of CD74highSiglecFlow neutrophils and suppress the generation of CD74lowSiglecFhigh neutrophils in the TME of IL-8-humanized NSCLC mice. The CD74highSiglecFlow neutrophils boost anti-tumor Tcell responses via antigen cross-presentation. Deleting CD74 in IL-8-humanized neutrophils impairs Tcell activation and exacerbates NSCLC progression, whereas a CD74 agonist enhances Tcell activation and the efficacy of anti-programmed cell death 1 (PD-1) or osimertinib therapies. Additionally, the CD74highCD63low neutrophils in the TME and peripheral blood of advanced NSCLC patients phenocopy the CD74highSiglecFlow neutrophils in the TME of NSCLC mice and correlate well with the responsiveness to anti-PD-1 plus chemotherapies. These findings demonstrate an IL-8-CD74high neutrophil axis that promotes anti-tumor immunity in NSCLC.

Next Stage of Peri-operative Treatment for Resectable, Locally Advanced Non-small Cell Lung Cancer

Next Stage of Peri-operative Treatment for Resectable, Locally Advanced Non-small Cell Lung Cancer

THE CLINICAL EFFECTIVENESS OF ADVANCED OR METASTATIC NON-SMALL CELL LUNG CANCER: A SYSTEMATIC REVIEW

Lung cancer presents a significant epidemiological and economic burden worldwide. This deadly type of cancer ranks second in incidence and first in mortality among all cancers. The rapid increase in new and expensive treatment options places a substantial financial strain on public healthcare systems. Given the limited healthcare resources, the economic evaluation of new cancer drugs is crucial for ensuring the sustainability of healthcare systems and improving patients' access to treatments. This study aims to systematically review health state utility values (HSUVs) associated with traditional chemotherapy and targeted therapies in the first-line treatment of advanced or metastatic non-small cell lung cancer (NSCLC). A search was conducted in PubMed, EMBASE, and BioMed databases to identify publications reporting HSUVs, and 10 studies were selected from 1319 based on predefined criteria. The study found that HSUVs for targeted therapies were consistently higher across all health states compared to traditional chemotherapy. The included publications provide a comprehensive framework of HSUVs applicable to this disease and highlight the need for more empirical research to obtain a broader range of HSUVs for NSCLC.

The Impact of Next-Generation Sequencing Workflows on Outcomes in Advanced Lung Cancer: A Retrospective Analysis at One Academic Health System.

Broad-based molecular testing with next-generation sequencing (NGS) is now the standard of care in advanced non-small cell lung cancer (NSCLC). Two approaches to molecular testing are (1) reflexive testing at pathologic NSCLC confirmation, often using an in-house molecular panel, and (2) send-out testing to private vendors, ordered by a clinician. This study explored the outcomes with reflex versus send-out testing. A retrospective chart review was conducted of patients diagnosed with de novo stage IV NSCLC in 2019 and 2020 at three hospitals in the same system, one academic hospital (Northwestern Memorial Hospital, or NMH) utilizing reflex, in-house NGS, and two community-based hospitals (Central DuPage Hospital, or CDH, and Delnor, or D) sending out tissue samples for testing. The outcomes assessed were the time from biopsy to results, biopsy to treatment, the incidence of first-line targetable mutations and the use of first-line targeted therapies, and overall survival. In total, 191 patients met the inclusion criteria, 85 at NMH, 106 at CDH + D, and in total, 131 in 2019 and 60 in 2020. The time to results was significantly shorter with reflexive NGS when compared with send-out testing; the time to treatment was also shorter but not statistically significant. At CDH + D, the time to results was significantly shorter with a limited panel than with comprehensive testing, but the time to treatment was similar. NGS testing rates were 95% at NMH and 84.5% at CDH + D (p = 0.009), with 31.0% at NMH receiving 1L targeted therapies versus 20.8% at CDH + D (p = 0.08). In 2019, the median time from biopsy to treatment was 35 days at NMH and 38 days at CDH and Delnor; in 2020, time to treatment was 26 days and 37 days, respectively. Overall survival trended longer in 2020 relative to 2019 independent of site. Reflexive NGS testing is associated with a shorter time to actionable results and higher rates of first-line targetable mutations than send-out testing. In practices with send-out testing, limited panels had slightly faster turnaround times but no difference in time to treatment. If resources allow, reflexive NGS should be considered in healthcare systems for patients with NSCLC.

Novel immunotherapeutic approaches in lung cancer: driving beyond programmed death-1/programmed death ligand-1 and cytotoxic T-lymphocyte-associated Protein-4.

In this review, our aim is to highlight the latest novel immunotherapeutic approaches for advanced nonsmall cell lung cancer (NSCLC) beyond anti-programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) and anti- cytotoxic T-lymphocyte-associated Protein-4 (CTLA4). Immune checkpoint inhibitors (ICIs) revolutionized the treatment of advanced NSCLC. Despite that, patients develop primary or acquired resistance to ICIs. The discovery of novel approaches represents both an unmet need and an opportunity to improve outcomes in these patients. We summarized the most relevant novel immune checkpoints, many of them in their early phase of testing, to provide a comprehensive overview of the state of the art of immunotherapy in NSCLC beyond PD-1/PD-L1 and CTL-4 inhibitors.

CIGB-300 internalizes and impairs viability of NSCLC cells lacking actionable targets by inhibiting casein kinase-2 signaling

Overall response rates in advanced Non-Small Cell Lung Cancer (NSCLC) remains low. Thus, novel molecular targets, tailored drugs and/or drug combinations are needed. Casein Kinase-2 (CK2) is a constitutively active and frequently over-expressed enzyme which fosters tumor survival, proliferation and metastasis. By using a clinical-grade and Cell Penetrating Peptide-based inhibitor coined as CIGB-300, we explore the anti-neoplastic effects caused by interruption of CK2 signaling in lung cancer cells lacking EGFR, ALK and ROS mutations. CIGB-300 penetrated and impaired viability and proliferation of Lung Adenocarcinoma (LUAD) (A549, NCI-H522) and Lung Squamous Carcinoma (LUSC) (NCI-H226 and SK-MES-1) cells in a dose-response manner. The differential activity could not be explained by overall peptide uptake or its subcellular distribution, as evidenced by flow cytometry and confocal microscopy. Upon internalization, CIGB-300 interacted with CK2 catalytic subunits (ɑ1/ɑ2) and CK2 substrates, thus impairing phosphorylation of enzyme substrates (CDC37s13, NPM1s125) and downstream proteins (RPS6s325/326). CK2 inhibition induced an early Reactive Oxygen Species (ROS) and mitochondrial membrane depolarization, which predates lung cancer cell death. Finally, intravenous injection of CIGB-300 in a cell line-based xenograft corroborated CIGB-300’s anti-tumor effects and suggested concurrent in situ reductions of CSNK2ɑ subunit and downstream RPS6s235/236 phosphorylation. Overall, CIGB-300 therapeutic hypothesis and antineoplastic effects demonstrated herein, further support the evaluation of this clinical-grade CK2 inhibitor in advanced NSCLC with limited therapeutic options.

Characterization of renal injury in non-squamous non-small cell lung cancer patients treated with pemetrexed: A single-center retrospective study.

Pemetrexed is a key therapeutic agent for advanced non-squamous non-small cell lung cancer (Nsq-NSCLC), yet it is associated with renal toxicity. This study aims to elucidate the incidence, risk factors, and survival impact of renal injury in patients with Nsq-NSCLC treated with pemetrexed. We conducted a retrospective study including 136 patients with Nsq-NSCLC treated with pemetrexed. Data on demographics, renal function, progression-free survival (PFS), and overall survival (OS) were collected. Renal injury was defined as a reduction above 25% in estimated glomerular filtration rate (eGFR) from baseline. Its associated risk factors were analyzed using logistic regression, and impact on survival was analyzed using log-rank test. The creatinine clearance rate (CCr) was calculated, and a CCr < 45 mL/min served as a contraindication for continuing pemetrexed. The study found a 31.6% (43/136) incidence of renal injury, with 9.6% (13/136) having CCr < 45 mL/min and discontinuing pemetrexed. Univariate and multivariate analyses identified factors significantly associated with increased renal injury risk including older age, use of cisplatin, and higher number of pemetrexed cycles. The patients with renal injury had a median PFS (mPFS) of 13.5 months and a median OS (mOS) of 36.0 months, while the patients without had an mPFS of 9.0 months and an mOS of 35.0 months, and these differences were not statistically significant. Renal injury is a considerable complication in patients with Nsq-NSCLC undergoing pemetrexed treatment, with age, platinum type, and pemetrexed treatment cycles as key risk factors. These findings highlight the necessity for careful renal monitoring in this patient population.

Clinical characteristics and prognostic factors of epidermal growth factor receptor-mutated non-small cell lung cancer transformed into small-cell lung cancer after treatment

Objective: To analyze the clinical characteristics and prognostic factors of non-small cell lung cancer (NSCLC) patients with sensitive epidermal growth factor receptor (EGFR) mutations who developed small cell lung cancer (SCLC) transformation after treatment with EGFR tyrosine kinase inhibitors (TKI). Methods: We conducted a retrospective collection of clinical data for 21 patients with advanced EGFR mutant NSCLC who developed SCLC transformation after EGFR-TKI treatment at Beijing Chest Hospital, Capital Medical University from January 2015 to December 2021. The clinical characteristics were summarized and the prognosis analysis was conducted. Patients were followed up until February 2024. The efficacy was evaluated using Solid Tumor Response Evaluation Criteria, and survival curves were plotted using the Kaplan-Meier method, and the log-rank test was used to compare the differences in survival time (OS) between limited stage and extensive stage in transformed SCLC patients. Cox proportional hazards model was used to analyze the influencing factors of survival after SCLC transformation. Results: Among the 21 patients, there were 5 males and 16 females, with an age range of 33-74 years old [(58.9±2.6) years old]. All 21 patients were adenocarcinoma with sensitive EGFR mutations. There were 18 cases (85.7%) with EGFR gene 19del mutation, including 1 case of 19del+anaplastic lymphoma kinase (ALK) mutation, and 3 cases of L858R mutation. Among the transformed SCLC, there were 11 cases of pure SCLC and 10 cases of mixed SCLC (coexisting of adenocarcinoma and small cell carcinoma components). The median time from diagnosis of NSCLC to SCLC transformation was 12.0 months (95%CI: 7.6-16.3 months). Among the 21 cases of SCLC transformation, there were 13 cases with the extensive stage and 8 cases with the limited stage. Among them, 16 patients received systemic chemotherapy based on etoposide, of which 13 cases could be evaluated for efficacy, 11 cases could be calculated for PFS. Five cases had partial remission, 5 cases were stable, 3 cases had disease progression, and 3 cases cloud not be evaluated. The median progression free survival time (PFS) was 4.8 months (95%CI: 2.8-6.8 months). The median survival time (OS) after SCLC transformation in 21 patients was 10.6 months (95%CI: 7.0-14.2 months), with a median OS of 8.8 months (95%CI: 6.3-11.4 months) for patients with the extensive stage and 27.5 months (95%CI: 9.6-34.4 months) for patients with the limited stage, with statistically significant differences (P=0.002). Cox proportional hazards model analysis showed that the limited stage after SCLC transformation was a protective factor for OS (HR=0.32, 95%CI: 0.12-0.73, P=0.010). The median OS of 21 patients from the diagnosis of lung cancer was 24.9 months (95%CI: 13.0-36.7 months). Conclusions: NSCLC patients with SCLC transformation are all adenocarcinomas, and the proportion of EGFR19del mutations is relatively high. After SCLC transformation, the standard chemotherapy regimen for SCLC is generally used for treatment. The OS after SCLC transformation is related to the stage, and the prognosis is better in the limited stage.

Perspectives on Drug Product Design Among Patients with Lung Cancer in the United Kingdom.

The use of oral anticancer medications has become more prevalent in cancer therapy. This is particularly the case in the management of advanced non-small cell lung cancer (NSCLC). However, when the treatment delivery interaction between the patient and the healthcare provider is removed, the risk of non-adherence increases. Insights into patient preferences can allow drug product formulation scientists to design more patient-centric medications that may promote an increase in adherence which, in turn, may lead to more beneficial health outcomes. We conducted an advisory board with patients with NSCLC in the United Kingdom to elicit and understand preferences for drug product attributes related to appearance, instructions, and modality. The advisory board was preceded by a quantitative preference survey that included three object-case best-worst scaling exercises and was followed by administering the same survey to a broader group of patients to confirm the results. Patients strongly prefer once-daily dosing over more frequent dosing, regardless of the number of pills because taking tablets or capsules multiple times each day can disrupt daily activities. In addition, patients place high importance on surface smoothness because a rough surface implies decreased swallowability. Finally, food restrictions involving directions regarding taking medication with or without food represent difficulties for patients with cancer. Results of the follow-up survey confirmed these results. Drug developers should attempt to limit the dosing of these medications to once-daily regimens, avoid surface roughness, and develop formulations that can be taken without regard to the timing of meals to the greatest extent possible.