New promises and challenges in the treatment of advanced non-small-cell lung cancer

The Lancet, Journal Year: 2024, Volume and Issue: 404(10454), P. 803 - 822

Published: Aug. 1, 2024

Language: Английский

---

Phase III KEYNOTE-789 Study of Pemetrexed and Platinum With or Without Pembrolizumab for Tyrosine Kinase Inhibitor‒Resistant, EGFR–Mutant, Metastatic Nonsquamous Non–Small Cell Lung Cancer

Journal of Clinical Oncology, Journal Year: 2024, Volume and Issue: 42(34), P. 4029 - 4039

Published: Aug. 22, 2024

PURPOSE Epidermal growth factor receptor ( EGFR ) tyrosine kinase inhibitors (TKIs) are standard first-line therapy for -mutant, metastatic non–small cell lung cancer (NSCLC); however, most patients experience disease progression. We report results from the randomized, double-blind, phase III KEYNOTE-789 study of pemetrexed and platinum–based chemotherapy with or without pembrolizumab TKI-resistant, nonsquamous NSCLC (ClinicalTrials.gov identifier: NCT03515837 ). METHODS Adults pathologically confirmed stage IV NSCLC, documented DEL19 L858R mutation, progression after EGFR-TKI treatment were randomly assigned 1:1 to 35 cycles 200 mg placebo once every 3 weeks plus four carboplatin cisplatin then maintenance pemetrexed. Dual primary end points progression-free survival (PFS) overall (OS). Final PFS testing was completed at second interim analysis (IA2; data cutoff, December 3, 2021); OS tested final (FA; January 17, 2023). Efficacy boundaries one-sided P = .0117 OS. RESULTS Four hundred ninety-two (n 245) 247). At IA2, median 5.6 months versus 5.5 (hazard ratio [HR], 0.80 [95% CI, 0.65 0.97]; .0122). FA, 15.9 14.7 months, respectively (HR, 0.84 0.69 1.02]; .0362). Grade ≥3 treatment-related adverse events occurred in 43.7% recipients 38.6% recipients. CONCLUSION Addition did not significantly prolong KEYNOTE-789.

Language: Английский

---

Ivonescimab Plus Chemotherapy in Non–Small Cell Lung Cancer With EGFR Variant

JAMA, Journal Year: 2024, Volume and Issue: 332(7), P. 561 - 561

Published: May 31, 2024

Importance For patients with non–small cell lung cancer whose disease progressed while receiving EGFR tyrosine kinase inhibitor (EGFR-TKI) therapy, particularly third-generation TKIs, optimal treatment options remain limited. Objective To compare the efficacy of ivonescimab plus chemotherapy alone for relapsed advanced or metastatic epidermal growth factor receptor ( ) variant. Design, Setting, and Participants Double-blind, placebo-controlled, randomized, phase 3 trial at 55 sites in China enrolled participants from January 2022 to November 2022; a total 322 eligible were enrolled. Interventions received (n = 161) placebo pemetrexed carboplatin once every weeks 4 cycles, followed by maintenance therapy pemetrexed. Main Outcomes Measures The primary end point was progression-free survival intention-to-treat population assessed an independent radiographic review committee (IRRC) per Response Evaluation Criteria Solid Tumors version 1.1. results first planned interim analysis are reported. Results Among groups, median age 59.6 vs 59.4 years 52.2% 50.9% female. As March 10, 2023, follow-up time 7.89 months. Median 7.1 (95% CI, 5.9-8.7) months group 4.8 4.2-5.6) (difference, 2.3 months; hazard ratio [HR], 0.46 [95% 0.34-0.62]; P < .001). prespecified subgroup showed benefit favoring over across almost all subgroups, including EGFR-TKI (HR, 0.48 CI 0.35-0.66]) those brain metastases 0.40 0.22-0.73]). objective response rate 50.6% 42.6%-58.6%) 35.4% 28.0%-43.3%) 15.6% 5.3%-26.0%]; .006). overall data not mature; cutoff, 69 (21.4%) had died. Grade higher treatment-emergent adverse events occurred 99 (61.5%) 79 (49.1%) group, most common which chemotherapy-related. immune-related 10 (6.2%) (2.5%) group. vascular endothelial factor–related 5 (3.1%) Conclusions Ivonescimab significantly improved tolerable safety profile TKI-treated cancer. Trial Registration ClinicalTrials.gov Identifier: NCT05184712

Language: Английский

---

Therapy for Stage IV Non–Small Cell Lung Cancer With Driver Alterations: ASCO Living Guideline, Version 2023.3

Journal of Clinical Oncology, Journal Year: 2024, Volume and Issue: 42(11), P. e1 - e22

Published: Feb. 28, 2024

To provide evidence-based recommendations for patients with stage IV non-small cell lung cancer driver alterations.

Language: Английский

---

Therapy for Stage IV Non–Small Cell Lung Cancer With Driver Alterations: ASCO Living Guideline, Version 2024.1

Journal of Clinical Oncology, Journal Year: 2024, Volume and Issue: 42(20), P. e44 - e59

Published: May 30, 2024

.

---

PD-1/PD-L1 inhibitors related adverse events: A bibliometric analysis from 2014 to 2024

Human Vaccines & Immunotherapeutics, Journal Year: 2025, Volume and Issue: 21(1)

Published: Jan. 6, 2025

Programmed cell death-1 (PD-1) inhibitors and programmed death ligand 1 (PD-L1) are considered effective alternatives for the primary treatment of recurrent metastatic cancers. However, they can induce various adverse events affecting multiple organ systems, potentially diminishing patients' quality life, even leading to interruptions. Adverse related PD-1/PD-L1 differ from those associated with CTLA-4 more commonly observed in solid tumors. This study aimed address knowledge gap regarding inhibitors. A visual bibliometric network was constructed using VOSviewer, CiteSpace, R software, Web Science Core Collection (WoSCC) quantitatively analyze this research field. Future directions were also explored. The USA ranked first publication count total citations. Over time, types transitioned case reports clinical trials. Research on nivolumab most prevalent. spectrum cancers treated by expanded beyond melanoma lung cancer include renal carcinoma, esophageal cancer, others. Common included pneumonitis, myasthenia gravis, vitiligo. There a significant increase multi-phase trials studies biomarkers. offers valuable insights potential collaborators institutions, highlighting trends management these has become refined standardized. Biomarker likely be key areas focus future studies.

Language: Английский

---

The changing treatment landscape of EGFR-mutant non-small-cell lung cancer

Nature Reviews Clinical Oncology, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 29, 2024

Language: Английский

---

Long-term survival of an ALK fusion lung adenocarcinoma patient with high mutation burden and microsatellite instability high: a case report

Anti-Cancer Drugs, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 5, 2025

Immune checkpoint blockage (ICB) therapy has shown minimal effectiveness in anaplastic lymphoma kinase (ALK)-positive nonsmall cell lung cancer (NSCLC) regardless of Programmed death-ligand 1 expression. ALK fusion accompanied by mismatch repair deficiency or microsatellite instability-high (MMRd/MSI-H) and high tumor mutation burden (TMB-H) are extremely rare NSCLC, the efficacy inhibitors ICB-based therapies is unclear. Here, we report case a 60-year-old female patient with metastatic adenocarcinoma EML4-ALK fusion, TMB-H, MMRd/MSI-H, pathogenic mutations TP53, MLH1, STK11. The experienced progression on initial iruplinalkib subsequent alectinib within 5 months. After failure third-line cisplatin-pemetrexed combined bevacizumab, she received sintilimab plus anlotinib which led to progression-free survival 6.5 She albumin-paclitaxel carboplatin achieved partial response after 6 developed adverse events one cycle treatment. Then was continued as maintenance due intolerance chemotherapy. therapy, treated lorlatinib still under follow-up overall more than 3 years. Our findings highlight therapeutic potential regimens patients MSI-H ALK-rearranged NSCLC.

Language: Английский

---

Immunotherapy efficacy between exon 19 deletion and exon 21 L858R mutation in advanced EGFR mutant non-small-cell lung cancer: a direct and indirect meta-analysis

Translational Lung Cancer Research, Journal Year: 2025, Volume and Issue: 14(2), P. 422 - 430

Published: Feb. 1, 2025

Immunotherapy (IO) exhibits poor therapeutic effect in epidermal growth factor receptor (EGFR) mutant advanced non-small-cell lung cancer (NSCLC). However, previous studies reveal different IO efficacy between exon 19 deletion (19 Del) and 21 L858R mutation (21 L858R). In this study, we aimed to evaluate the difference patients with EGFR Del L858R. data of response rate, disease control rate (DCR), progression-free survival (PFS), overall (OS) stratified by subtypes were extracted synthesized on random-effect model using odds ratios (ORs) for dichotomous hazard (HRs) 95% confidence interval (CI). Efficacy comparisons estimated through direct indirect methods respectively. A total 15 that involved 1,209 EGFR-mutant NSCLC treatment included Del, n=676; L858R, n=533). Based from 11 meta-analysis, had shorter PFS (HR =1.55; CI: 1.21-1.98; P=0.001) OS =1.36; 1.04-1.78; P=0.02) poorer DCR (OR =0.51; 0.29-0.87; than those significantly. Indirect meta-analysis four trials showed same result significantly =1.50; 1.09-2.07; P=0.01) Subgroup analyses also similar tendency more clinical benefit compared no matter whether monotherapy or combination. For patients, superior Del.

Language: Английский

---

Multi-omics and artificial intelligence predict clinical outcomes of immunotherapy in non-small cell lung cancer patients

Clinical and Experimental Medicine, Journal Year: 2024, Volume and Issue: 24(1)

Published: March 30, 2024

Abstract In recent years, various types of immunotherapy, particularly the use immune checkpoint inhibitors targeting programmed cell death 1 or ligand (PD-L1), have revolutionized management and prognosis non-small lung cancer. PD-L1 is frequently used as a biomarker for predicting likely benefit immunotherapy patients. However, some patients receiving high response rates despite having low levels PD-L1. Therefore, identification this group extremely important to improve prognosis. The tumor microenvironment contains tumor, stromal, infiltrating cells with its composition differing significantly within tumors, between individuals. omics approach aims provide comprehensive assessment each patient through high-throughput extracted features, promising more characterization complex ecosystem. features identified by methods are present analytical challenges clinicians data scientists. It thus feasible that artificial intelligence could assist in beyond human discernment well performance repetitive tasks. paper, we review prediction efficacy different biomarkers (genomic, transcriptomic, proteomic, microbiomic, radiomic), together future directions these fields.

Language: Английский

---