Perioperative Pembrolizumab for Early-Stage Non–Small-Cell Lung Cancer

New England Journal of Medicine, Год журнала: 2023, Номер 389(6), С. 491 - 503

Опубликована: Июнь 3, 2023

Among patients with resectable early-stage non–small-cell lung cancer (NSCLC), a perioperative approach that includes both neoadjuvant and adjuvant immune checkpoint inhibition may provide benefit beyond either alone. Download PDF of the Research Summary. We conducted randomized, double-blind, phase 3 trial to evaluate pembrolizumab in NSCLC. Participants stage II, IIIA, or IIIB (N2 stage) NSCLC were assigned 1:1 ratio receive (200 mg) placebo once every weeks, each which was given cisplatin-based chemotherapy for 4 cycles, followed by surgery weeks up 13 cycles. The dual primary end points event-free survival (the time from randomization first occurrence local progression precluded planned surgery, unresectable tumor, recurrence, death) overall survival. Secondary included major pathological response, complete safety. A total 397 participants group, 400 group. At prespecified interim analysis, median follow-up 25.2 months. Event-free at 24 months 62.4% group 40.6% (hazard progression, death, 0.58; 95% confidence interval [CI], 0.46 0.72; P<0.001). estimated 24-month 80.9% 77.6% (P=0.02, did not meet significance criterion). response occurred 30.2% 11.0% those (difference, 19.2 percentage points; CI, 13.9 24.7; P<0.0001; threshold, P=0.0001), 18.1% 4.0%, respectively 14.2 10.1 18.7; P=0.0001). Across all treatment phases, 44.9% 37.3% had treatment-related adverse events grade higher, including 1.0% 0.8%, respectively, who 5 events. resectable, NSCLC, plus resection significantly improved survival, as compared alone surgery. Overall differ between groups this analysis. (Funded Merck Sharp Dohme; KEYNOTE-671 ClinicalTrials.gov number, NCT03425643.) QUICK TAKE VIDEO SUMMARYNeoadjuvant Pembrolizumab Lung Cancer 02:12

Язык: Английский

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Oncogene-addicted metastatic non-small-cell lung cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up

Annals of Oncology, Год журнала: 2023, Номер 34(4), С. 339 - 357

Опубликована: Янв. 23, 2023

Язык: Английский

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Leveraging Large Language Models for Decision Support in Personalized Oncology

JAMA Network Open, Год журнала: 2023, Номер 6(11), С. e2343689 - e2343689

Опубликована: Ноя. 17, 2023

Clinical interpretation of complex biomarkers for precision oncology currently requires manual investigations previous studies and databases. Conversational large language models (LLMs) might be beneficial as automated tools assisting clinical decision-making.

Язык: Английский

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Non-small-cell lung cancer

Nature Reviews Disease Primers, Год журнала: 2024, Номер 10(1)

Опубликована: Сен. 26, 2024

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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Tumor Treating Fields therapy with standard systemic therapy versus standard systemic therapy alone in metastatic non-small-cell lung cancer following progression on or after platinum-based therapy (LUNAR): a randomised, open-label, pivotal phase 3 study

The Lancet Oncology, Год журнала: 2023, Номер 24(9), С. 1002 - 1017

Опубликована: Авг. 29, 2023

Язык: Английский

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KRAS G12C in advanced NSCLC: Prevalence, co-mutations, and testing

Lung Cancer, Год журнала: 2023, Номер 184, С. 107293 - 107293

Опубликована: Июль 12, 2023

KRAS is the most commonly mutated oncogene in advanced, non-squamous, non-small cell lung cancer (NSCLC) Western countries. Of various mutants, G12C common variant (~40%), representing 10-13% of advanced non-squamous NSCLC. Recent regulatory approvals KRASG12C-selective inhibitors sotorasib and adagrasib for patients with or metastatic NSCLC harboring KRASG12C have transformed into a druggable target. In this review, we explore evolving role from prognostic to predictive biomarker NSCLC, discussing biology, real-world prevalence, clinical relevance co-mutations, approaches molecular testing. Real-world evidence demonstrates significant geographic differences prevalence (8.9-19.5% US, 9.3-18.4% Europe, 6.9-9.0% Latin America, 1.4-4.3% Asia) Additionally, body data pertaining co-mutations such as STK11, KEAP1, TP53 increasing. evidence, G12C-mutant was associated 10.3-28.0%, 6.3-23.0%, 17.8-50.0% patients, respectively. Whilst are currently approved use second-line setting beyond advanced/metastatic testing reporting should be included routine prior first-line therapy. test results clearly documented patients' health records actionability at progression. Where available, next-generation sequencing recommended facilitate simultaneous potentially actionable biomarkers single run conserve tissue. Results inform decisions treating G12C-mutated

Язык: Английский

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Four-year clinical update and treatment switching-adjusted outcomes with first-line nivolumab plus ipilimumab with chemotherapy for metastatic non-small cell lung cancer in the CheckMate 9LA randomized trial

Journal for ImmunoTherapy of Cancer, Год журнала: 2024, Номер 12(2), С. e008189 - e008189

Опубликована: Фев. 1, 2024

Background In CheckMate 9LA, nivolumab plus ipilimumab with chemotherapy prolonged overall survival (OS) versus regardless of tumor PD-L1 expression or histology. We report updated efficacy and safety in all randomized patients a minimum 4-year follow-up an exploratory treatment-switching adjustment analysis treated who received subsequent immunotherapy. Methods Adults stage IV/recurrent non-small cell lung cancer (NSCLC), no sensitizing EGFR/ALK alterations, ECOG performance status ≤1 were 1:1 to 360 mg every 3 weeks 1 mg/kg 6 (two cycles) (four cycles, optional maintenance pemetrexed for the nonsquamous population). Assessments included OS, progression-free survival, objective response rate. Exploratory analyses by histology discontinued due treatment-related adverse events (TRAEs), using inverse probability censoring weighting. Results With 47.9-month continued prolong OS over (HR 0.74, 95% CI 0.63 0.87; rate: 21% 16%), (95% CI): PD-L1<1%, 0.66 (0.50 0.86) ≥1%, 0.74 (0.60 0.92)) (squamous, 0.64 (0.48 0.84) non-squamous, 0.80 (0.66 0.97)). components TRAEs (n=61), rate was 41%. 36% receiving immunotherapy arm, estimated HR 0.55 0.80). No new signals observed. Conclusions this update, have long-term, durable benefit and/or A greater relative observed after use arm. These results further support as first-line treatment metastatic/recurrent NSCLC, including those PD-L1<1% squamous histology, populations high unmet needs.

Язык: Английский

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Datopotamab Deruxtecan Versus Docetaxel for Previously Treated Advanced or Metastatic Non–Small Cell Lung Cancer: The Randomized, Open-Label Phase III TROPION-Lung01 Study

Journal of Clinical Oncology, Год журнала: 2024, Номер unknown

Опубликована: Сен. 9, 2024

PURPOSE The randomized, open-label, global phase III TROPION-Lung01 study compared the efficacy and safety of datopotamab deruxtecan (Dato-DXd) versus docetaxel in patients with pretreated advanced/metastatic non–small cell lung cancer (NSCLC). METHODS Patients received Dato-DXd 6 mg/kg or 75 mg/m 2 once every 3 weeks. Dual primary end points were progression-free survival (PFS) overall (OS). Objective response rate, duration response, secondary points. RESULTS In total, 299 305 randomly assigned to receive docetaxel, respectively. median PFS was 4.4 months (95% CI, 4.2 5.6) 3.7 2.9 4.2) (hazard ratio [HR], 0.75 [95% 0.62 0.91]; P = .004). OS 12.9 11.0 13.9) 11.8 10.1 12.8), respectively (HR, 0.94 0.78 1.14]; .530). prespecified nonsquamous histology subgroup, 5.5 3.6 0.63 0.51 0.79]) 14.6 12.3 0.84 0.68 1.05]). squamous 2.8 3.9 1.41 0.95 2.08]) 7.6 9.4 1.32 0.91 1.92]). Grade ≥3 treatment-related adverse events occurred 25.6% 42.1% patients, any-grade adjudicated drug-related interstitial disease/pneumonitis 8.8% 4.1% groups, CONCLUSION significantly improved NSCLC, driven by histology. showed a numerical benefit but did not reach statistical significance. No unexpected signals observed.

Язык: Английский

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Pembrolizumab Plus Chemotherapy for Metastatic NSCLC With Programmed Cell Death Ligand 1 Tumor Proportion Score Less Than 1%: Pooled Analysis of Outcomes After Five Years of Follow-Up

Journal of Thoracic Oncology, Год журнала: 2024, Номер 19(8), С. 1228 - 1241

Опубликована: Апрель 18, 2024

Язык: Английский

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