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

The Lancet, Год журнала: 2024, Номер 404(10454), С. 803 - 822

Опубликована: Авг. 1, 2024

Язык: Английский

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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, Год журнала: 2024, Номер 42(34), С. 4029 - 4039

Опубликована: Авг. 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.

Язык: Английский

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Osimertinib treatment based on plasma T790M monitoring in patients with EGFR-mutant non-small-cell lung cancer (NSCLC): EORTC Lung Cancer Group 1613 APPLE phase II randomized clinical trial

Annals of Oncology, Год журнала: 2023, Номер 34(5), С. 468 - 476

Опубликована: Фев. 28, 2023

Язык: Английский

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Forget lung, breast or prostate cancer: why tumour naming needs to change

Nature, Год журнала: 2024, Номер 626(7997), С. 26 - 29

Опубликована: Янв. 31, 2024

Язык: Английский

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Trastuzumab deruxtecan in patients with solid tumours harbouring specific activating HER2 mutations (DESTINY-PanTumor01): an international, phase 2 study

The Lancet Oncology, Год журнала: 2024, Номер 25(6), С. 707 - 719

Опубликована: Май 3, 2024

Язык: Английский

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Future perspective for the application of predictive biomarker testing in advanced stage non-small cell lung cancer

The Lancet Regional Health - Europe, Год журнала: 2024, Номер 38, С. 100839 - 100839

Опубликована: Март 1, 2024

For patients with advanced stage non-small cell lung cancer (NSCLC), treatment strategies have changed significantly due to the introduction of targeted therapies and immunotherapy. In last few years, we seen an explosive growth newly introduced in oncology this development is expected continue future. Besides primary targetable aberrations, emerging diagnostic biomarkers also include relevant co-occurring mutations resistance mechanisms involved disease progression, that impact on optimal management. To accommodate testing pending biomarkers, it necessary establish routine large-panel next-generation sequencing (NGS) for all NSCLC. cost-effectiveness accessibility, recommended implement predictive molecular using NGS a dedicated, centralized expert laboratory within regional network. The central center should host Molecular Tumor Board function as hub interpretation rare complex results clinical decision-making.

Язык: Английский

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Developments in predictive biomarker testing and targeted therapy in advanced stage non-small cell lung cancer and their application across European countries

The Lancet Regional Health - Europe, Год журнала: 2024, Номер 38, С. 100838 - 100838

Опубликована: Март 1, 2024

In the past two decades, treatment of metastatic non-small cell lung cancer (NSCLC), has undergone significant changes due to introduction targeted therapies and immunotherapy. These advancements have led need for predictive molecular tests identify patients eligible therapy. This review provides an overview development current application biomarker testing in European with advanced stage NSCLC. Using data from eleven countries, we conclude that recommendations are incorporated national guidelines across Europe, although there differences their comprehensiveness. Moreover, availability recently EMA-approved varies between countries. Unfortunately, routine assessment national/regional rates is limited. As a result, it remains uncertain which proportion NSCLC Europe receive adequate testing. Lastly, Molecular Tumor Boards (MTBs) discussion test results widely implemented, but composition functioning lacking. The establishment MTB can provide framework interpreting rare or complex mutations, facilitating appropriate decision-making, ensuring quality control.

Язык: Английский

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Sotorasib in KRAS G12C-mutated non-small cell lung cancer: A multicenter real-world experience from the compassionate use program in Germany

European Journal of Cancer, Год журнала: 2024, Номер 201, С. 113911 - 113911

Опубликована: Фев. 14, 2024

BackgroundSotorasib is a first-in-class KRAS p.G12C-inhibitor that has entered clinical trials in pretreated patients with non-small cell lung cancer (NSCLC) 2018. First response rates were promising the CodeBreaK trials. It remains unclear whether to sotorasib and outcomes differ real-world setting when including underrepresented trials.MethodsPatients p.G12C-mutated advanced or metastatic NSCLC received within German multicenter compassionate use program between 2020 2022. Data on efficacy, tolerability, survival analyzed full cohort subgroups of special interest such as co-occurring mutations across PD-L1 expression levels.ResultsWe 163 who after median two treatment lines (range, 0 7). Every fourth patient had poor performance status 38% brain metastases (BM). The objective rate was 38.7%. overall 9.8 months (95% CI, 6.5 not reached). Median (rw) progression-free 4.8 (9% 3.9 5.9). Dose reductions permanent discontinuation necessary 35 (21.5%) 7 (4.3%) patients, respectively. Efficacy seems be influenced by KEAP1 mutation. associated an inferior survival. Other factors BM, STK11, TP53 no impact survival.ConclusionFirst results from population confirm efficacy for NSCLC. Patients seem derive less benefit.

Язык: Английский

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Challenges and controversies in resectable non-small cell lung cancer: a clinician’s perspective

The Lancet Regional Health - Europe, Год журнала: 2024, Номер 38, С. 100841 - 100841

Опубликована: Март 1, 2024

The treatment landscape of resectable early-stage non-small cell lung cancer (NSCLC) is transforming due to the approval novel adjuvant and neoadjuvant systemic treatments. European Medicines Agency (EMA) recently approved osimertinib, atezolizumab, pembrolizumab, nivolumab combined with chemotherapy, other agents or new indications may follow soon. Despite encouraging results, many unaddressed questions remain. Moreover, transformed paradigm in NSCLC can pose major challenges healthcare systems magnify existing disparities care as differences reimbursement vary across different countries. This Viewpoint discusses controversies how inequalities access these treatments could be addressed.

Язык: Английский

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Iruplinalkib (WX-0593) Versus Crizotinib in ALK TKI-Naive Locally Advanced or Metastatic ALK-Positive NSCLC: Interim Analysis of a Randomized, Open-Label, Phase 3 Study (INSPIRE)

Journal of Thoracic Oncology, Год журнала: 2024, Номер 19(6), С. 912 - 927

Опубликована: Янв. 25, 2024

J o u r n a l P e -p f patients in the iruplinalkib group (median PFS, 27.7 months [95% CI, crizotinib group; HR, 0.34 [98.02% 0.23-0.52];p<0.0001).The ORR assessed by IRC was 93.0% (95% 87.5-96.6) and 89.3% 83.1-93.7) group.The intracranial 90.9% (10/11, 95% 58.7-99.8) 60.0% (9/15, 32.3-83.7) for with measurable baseline CNS metastases.Incidence of grade 3 or 4 treatment-related adverse events 51.7% 49.7% group.Interpretation: Iruplinalkib demonstrated significantly improved PFS antitumor activity versus crizotinib.Iruplinalkib may be new treatment option advanced ALK positive TKI-naïve NSCLC.

Язык: Английский

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