Recommendations for the use of next-generation sequencing (NGS) for patients with advanced cancer in 2024: a report from the ESMO Precision Medicine Working Group

Annals of Oncology, Год журнала: 2024, Номер 35(7), С. 588 - 606

Опубликована: Май 27, 2024

Advancements in the field of precision medicine have prompted European Society for Medical Oncology (ESMO) Precision Medicine Working Group to update recommendations use tumour next-generation sequencing (NGS) patients with advanced cancers routine practice.

Язык: Английский

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Amivantamab plus Lazertinib in Previously Untreated EGFR -Mutated Advanced NSCLC

New England Journal of Medicine, Год журнала: 2024, Номер 391(16), С. 1486 - 1498

Опубликована: Июнь 26, 2024

BackgroundAmivantamab plus lazertinib (amivantamab–lazertinib) has shown clinically meaningful and durable antitumor activity in patients with previously untreated or osimertinib-pretreated EGFR (epidermal growth factor receptor)–mutated advanced non–small-cell lung cancer (NSCLC).MethodsIn a phase 3, international, randomized trial, we assigned, 2:2:1 ratio, EGFR-mutated (exon 19 deletion L858R), locally metastatic NSCLC to receive amivantamab–lazertinib (in an open-label fashion), osimertinib blinded fashion, assess the contribution of treatment components). The primary end point was progression-free survival group as compared group, assessed by independent central review.ResultsOverall, 1074 underwent randomization (429 amivantamab–lazertinib, 429 osimertinib, 216 lazertinib). median significantly longer than (23.7 vs. 16.6 months; hazard ratio for disease progression death, 0.70; 95% confidence interval [CI], 0.58 0.85; P<0.001). An objective response observed 86% (95% CI, 83 89) 85% those 81 88) group; among confirmed (336 314 group), duration 25.8 months 20.1 could not be estimated) 16.8 14.8 18.5), respectively. In planned interim overall analysis death 0.80 0.61 1.05). Predominant adverse events were EGFR-related toxic effects. incidence discontinuation all agents due treatment-related 10% 3% osimertinib.ConclusionsAmivantamab–lazertinib showed superior efficacy first-line NSCLC. (Funded Janssen Research Development; MARIPOSA ClinicalTrials.gov number, NCT04487080.)

Язык: Английский

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

JAMA, Год журнала: 2024, Номер 332(7), С. 561 - 561

Опубликована: Май 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 &amp;lt; .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

Язык: Английский

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Bispecific and multispecific antibodies in oncology: opportunities and challenges

Nature Reviews Clinical Oncology, Год журнала: 2024, Номер 21(7), С. 539 - 560

Опубликована: Май 31, 2024

Язык: Английский

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Subcutaneous versus Intravenous Amivantamab, both in Combination with Lazertinib, in Refractory EGFR-mutated NSCLC: Primary Results from the Phase 3 PALOMA-3 Study

Journal of Clinical Oncology, Год журнала: 2024, Номер 42(30), С. 3593 - 3605

Опубликована: Июнь 10, 2024

PURPOSE Phase III studies of intravenous amivantamab demonstrated efficacy across epidermal growth factor receptor ( EGFR )–mutated advanced non–small cell lung cancer (NSCLC). A subcutaneous formulation could improve tolerability and reduce administration time while maintaining efficacy. PATIENTS AND METHODS Patients with -mutated NSCLC who progressed after osimertinib platinum-based chemotherapy were randomly assigned 1:1 to receive or amivantamab, both combined lazertinib. Coprimary pharmacokinetic noninferiority end points trough concentrations (C ; on cycle-2-day-1 cycle-4-day-1) cycle-2 area under the curve (AUC D1-D15 ). Key secondary objective response rate (ORR) progression-free survival (PFS). Overall (OS) was a predefined exploratory point. RESULTS Overall, 418 patients underwent random assignment (subcutaneous group, n = 206; 212). Geometric mean ratios C for 1.15 (90% CI, 1.04 1.26) at 1.42 1.27 1.61) cycle-4-day-1; AUC 1.03 0.98 1.09). ORR 30% in 33% group; median PFS 6.1 4.3 months, respectively. OS significantly longer versus group (hazard ratio death, 0.62; 95% 0.42 0.92; nominal P .02). Fewer experienced infusion-related reactions (IRRs; 13% v 66%) venous thromboembolism (9% 14%) group. Median first infusion reduced 4.8 minutes (range, 0-18) 5 hours 0.2-9.9) amivantamab. During cycle-1-day-1, 85% 52% groups, respectively, considered treatment convenient; end-of-treatment rates 35%, CONCLUSION Subcutaneous amivantamab-lazertinib amivantamab-lazertinib, offering consistent safety profile IRRs, increased convenience, prolonged survival.

Язык: Английский

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Therapeutic advances of targeting receptor tyrosine kinases in cancer

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Авг. 14, 2024

Abstract Receptor tyrosine kinases (RTKs), a category of transmembrane receptors, have gained significant clinical attention in oncology due to their central role cancer pathogenesis. Genetic alterations, including mutations, amplifications, and overexpression certain RTKs, are critical creating environments conducive tumor development. Following discovery, extensive research has revealed how RTK dysregulation contributes oncogenesis, with many subtypes showing dependency on aberrant signaling for proliferation, survival progression. These findings paved the way targeted therapies that aim inhibit crucial biological pathways cancer. As result, RTKs emerged as primary targets anticancer therapeutic Over past two decades, this led synthesis validation numerous small molecule kinase inhibitors (TKIs), now effectively utilized treating various types. In manuscript we provide comprehensive understanding context We explored alterations specific receptors across different malignancies, special dedicated examination current inhibitors, highlighting potential therapies. By integrating latest evidence, seek elucidate pivotal biology efficacy inhibition promising treatment outcomes.

Язык: Английский

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Amivantamab plus lazertinib versus osimertinib in first-line EGFR-mutant advanced non-small-cell lung cancer with biomarkers of high-risk disease: a secondary analysis from MARIPOSA

Annals of Oncology, Год журнала: 2024, Номер 35(9), С. 805 - 816

Опубликована: Июнь 26, 2024

Amivantamab-lazertinib significantly prolonged progression-free survival (PFS) versus osimertinib in patients with epidermal growth factor receptor (EGFR)-mutant advanced non-small-cell lung cancer [NSCLC; hazard ratio (HR) 0.70; P < 0.001], including those a history of brain metastases (HR 0.69). Patients TP53 co-mutations, detectable circulating tumor DNA (ctDNA), baseline liver metastases, and without ctDNA clearance on treatment have poor prognoses. We evaluated outcomes these high-risk subgroups.

Язык: Английский

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

Journal of Clinical Oncology, Год журнала: 2024, Номер 42(11), С. e1 - e22

Опубликована: Фев. 28, 2024

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

Язык: Английский

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The study of primary and acquired resistance to first-line osimertinib to improve the outcome of EGFR-mutated advanced Non-small cell lung cancer patients: the challenge is open for new therapeutic strategies

Critical Reviews in Oncology/Hematology, Год журнала: 2024, Номер 196, С. 104295 - 104295

Опубликована: Фев. 20, 2024

The development of targeted therapy in epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) patients has radically changed their clinical perspectives. Current first-line standard treatment for advanced disease is commonly considered third-generation tyrosine kinase inhibitors (TKI), osimertinib. study primary and acquired resistance to front-line osimertinib one the main burning issues further improve patients' outcome. Great heterogeneity been depicted terms duration benefit pattern progression this might be related molecular factors including subtypes EGFR mutations concomitant genetic alterations. Acquired can categorized into two classes: EGFR-dependent EGFR-independent mechanisms specific have demonstrated. purpose manuscript provide a comprehensive overview literature about osimertinib, from perspective therefore relationship emerging therapeutic approaches.

Язык: Английский

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