Neoadjuvant sintilimab plus chemotherapy in EGFR-mutant NSCLC: Phase 2 trial interim results (NEOTIDE/CTONG2104)

Cell Reports Medicine, Год журнала: 2024, Номер 5(7), С. 101615 - 101615

Опубликована: Июнь 18, 2024

The clinical efficacy of neoadjuvant immunotherapy plus chemotherapy remains elusive in localized epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). Here, we report interim results a Simon's two-stage design, phase 2 trial using sintilimab with carboplatin and nab-paclitaxel resectable EGFR-mutant NSCLC. All 18 patients undergo radical surgery, one patient experiencing surgery delay. Fourteen exhibit confirmed radiological response, 44% achieving major pathological response (MPR) no complete (pCR). Similar genomic alterations are observed before after treatment without influencing the subsequent EGFR-tyrosine kinase inhibitors (TKIs) vitro. Infiltration T (TCR) clonal expansion CCR8+ regulatory (Treg)hi/CXCL13+ exhausted (Tex)lo cells define subtype NSCLC highly resistant to immunotherapy, phenotype potentially serving as promising signature predict efficacy. Informed circulating tumor DNA (ctDNA) detection could help identify nonresponsive immunochemotherapy. These findings provide supportive data for utilization immunochemotherapy insight into immune resistance

Язык: Английский

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Drug Resistance in Late-Stage Epidermal Growth Factor Receptor (EGFR)-Mutant Non-Small Cell Lung Cancer Patients After First-Line Treatment with Tyrosine Kinase Inhibitors

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(5), С. 2042 - 2042

Опубликована: Фев. 26, 2025

The development of tyrosine kinase inhibitors (TKIs) for late-stage epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) represented a drastic change in the treatment cancer. Drug resistance develops after certain period first-line TKI treatment, which has led to decades changing guidelines EGFR-mutant NSCLC. This study discussed potential mechanisms drug against and successive strategies. Next-generation sequencing (NGS) may play role evaluation treatment. Emerging combination regimens ongoing trials were discussed. Potential future strategies management proposed this study.

Язык: Английский

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Perioperative Treatment Strategies in EGFR-Mutant Early-Stage NSCLC: Current Evidence and Future Challenges

Journal of Thoracic Oncology, Год журнала: 2023, Номер 19(2), С. 199 - 215

Опубликована: Сен. 30, 2023

Язык: Английский

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Tissue- and liquid-biopsy based NGS profiling in advanced non-small-cell lung cancer in a real-world setting: the IMMINENT study

Frontiers in Oncology, Год журнала: 2024, Номер 14

Опубликована: Июль 9, 2024

Introduction To date, for all non-small cell lung cancer (NSCLC) cases, it is recommended to test driver alterations identify actionable therapeutic targets. In this light, comprehensive genomic profiling (CGP) with next generation sequencing (NGS) has progressively gained increasing importance in clinical practice. Here, the aim of assessing distribution and real-world frequency gene their correlation patient characteristics, we present outcomes obtained using FoundationOne (F1CDx) FoundationLiquid CDx (F1L/F1LCDx) NGS-based a nationwide initiative advanced NSCLC patients. Methods F1CDx (324 genes) was used tissue samples, F1L (70 or F1LCDx liquid biopsy, aiming explore occurrence molecular aNSCLC relationship patients’ characteristics. Results Overall, 232 patients from 11 Institutions were gathered [median age 63 years; never/former current smokers 29.3/65.9%; adenocarcinoma/squamous 79.3/12.5%; F1CDx/F1L+F1LCDx 59.5/40.5%]. Alterations found 170 different genes. Median number mutated genes per sample 4 (IQR 3–6) 2 1–3) F1L/F1LCDx cohorts, respectively. TP53 (58%), KRAS (22%), CDKN2A/B (19%), STK11 (17%) most frequently detected. Actionability rates (tier I II) comparable: 36.2% vs. 34% ctDNA NGS assays (29.5% 40.9% F1LCDx, respectively). KEAP1 significantly associated , so as RB1 . tumor mutational burden 6 3–10) higher smokers. OS metastatic diagnosis 23 months 18.5–19.5) lower harboring ≥3 mutations. Conditional three-year survival probabilities increased over time profiled at initial exceeded those individuals tested later history after 12 months. Conclusion This study confirms that on blood samples offers valuable predictive prognostic insights.

Язык: Английский

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First-line concomitant EGFR-TKI + chemotherapy versus EGFR-TKI alone for advanced EGFR -mutated NSCLC: a meta-analysis of randomized phase III trials

Expert Review of Anticancer Therapy, Год журнала: 2024, Номер 24(8), С. 775 - 780

Опубликована: Май 30, 2024

A tyrosine-kinase inhibitor (TKI) is indicated as a first-line treatment for patients with non-small-cell lung cancer (NSCLC) harboring an epidermal growth-factor - receptor (

Язык: Английский

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Current status of molecular diagnostics for lung cancer

Exploration of Targeted Anti-tumor Therapy, Год журнала: 2024, Номер 5(3), С. 742 - 765

Опубликована: Июнь 27, 2024

The management of lung cancer (LC) requires the analysis a diverse spectrum molecular targets, including kinase activating mutations in EGFR, ERBB2 (HER2), BRAF and MET oncogenes, KRAS G12C substitutions, ALK, ROS1, RET NTRK1-3 gene fusions. Administration immune checkpoint inhibitors (ICIs) is based on immunohistochemical (IHC) PD-L1 expression determination tumor mutation burden (TMB). Clinical characteristics patients, particularly age, gender smoking history, significantly influence probability finding above targets: for example, LC young patients characterized by high frequency rearrangements, while heavy smokers often have and/or TMB. Proper selection first-line therapy influences overall treatment outcomes, therefore, majority these tests need to be completed within no more than 10 working days. Activating events MAPK signaling pathway are mutually exclusive, hence, fast single-gene testing remains an option some laboratories. RNA next-generation sequencing (NGS) capable detecting entire repertoire druggable alterations, therefore it gradually becoming dominating technology diagnosis.

Язык: Английский

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Effects of Tp53 Gene Mutations on the Survival of Non-Small Cell Lung Cancer (NSCLC); A Short Review

Cancer Management and Research, Год журнала: 2025, Номер Volume 17, С. 65 - 82

Опубликована: Янв. 1, 2025

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths worldwide.Mutations within TP53 gene represent critical molecular events in NSCLC, contributing to tumorigenesis pulmonary epithelial tissues.TP53 a widely researched prognostic indicator and pathological investigations have revealed weak mild negative predictive effect for TP53.Mutated p53 protein may some pro-oncogenic impact, variations change tumor inhibitors into oncogenes.The diverse mutational spectrum NSCLC with different mutations linked varied treatment responses.In contrast, first-line chemotherapeutics this progress are limited, however, randomized trials new shown significant survival benefits.This review highlighted influence on pathological-sensitivity overall outcomes NSCLC.Further research needed explore mutation-specific pathways their effects progression effectiveness.

Язык: Английский

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Prognostic and predictive effects of TP53 co-mutation in patients with non-small cell lung cancer with rare treatable driver mutations

Lung Cancer, Год журнала: 2025, Номер 204, С. 108452 - 108452

Опубликована: Фев. 16, 2025

Язык: Английский

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Real-world prognostic factors for first-line EGFR-TKI efficacy in advanced NSCLC patients harboring EGFR 21L858R mutation

Global Medical Genetics, Год журнала: 2025, Номер unknown, С. 100051 - 100051

Опубликована: Фев. 1, 2025

This study aimed to investigate the prognostic factors for treatment efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in non-small cell lung cancer (NSCLC) patients with EGFR exon 21 L858R mutation. The enrolled advanced L858R-mutant NSCLC who received first-line EGFR-TKI between January 2019 and April 2024. Cox regression analyses were performed identify from clinical characteristics concomitant genetic alterations that influenced progression-free survival (PFS) overall (OS). According a cohort 120 patients, we found more metastatic organs (≥3 organs), specific patterns (liver bone involvement), concurrent TP53 mutations, worse Eastern Cooperative Oncology Group Performance Status (ECOG PS) associated shorter PFS. And ECOG PS was an independent predictive Similarly, ≥ 3 (HR, 2.719; 95 % CI, 1.386-5.333; p = 0.004), 2 10.756; 4.002-28.906; < 0.001), body mass index (BMI)＞24 kg/m2 0.335; 0.147-0.760; 0.009) OS. We also observed harboring co-mutations demonstrated significantly inferior PFS compared their wild-type counterparts (13.7 months vs. 18.8 months; 0.006). identified several response EGFR-TKIs mutation respective These findings could enable personalized therapeutic assessment facilitate decision-making treated EGFR-TKIs.

Язык: Английский

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Impact of TP53 co-mutation on clinicopathological features, prognosis, recurrence patterns, and the efficacy of EGFR-TKI treatment after recurrence in resected early-stage EGFR-mutated lung adenocarcinoma

Clinical Lung Cancer, Год журнала: 2025, Номер unknown

Опубликована: Апрель 1, 2025

Язык: Английский

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