Pembrolizumab in combination with gemcitabine and cisplatin compared with gemcitabine and cisplatin alone for patients with advanced biliary tract cancer (KEYNOTE-966): a randomised, double-blind, placebo-controlled, phase 3 trial

The Lancet, Journal Year: 2023, Volume and Issue: 401(10391), P. 1853 - 1865

Published: April 16, 2023

Language: Английский

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Pembrolizumab Plus Chemotherapy in Squamous Non–Small-Cell Lung Cancer: 5-Year Update of the Phase III KEYNOTE-407 Study

Journal of Clinical Oncology, Journal Year: 2023, Volume and Issue: 41(11), P. 1999 - 2006

Published: Feb. 3, 2023

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary point, may be published when key planned co-primary or secondary analyses are not yet available. Trial Updates provide an opportunity to disseminate additional results from studies, in JCO elsewhere, for which point has already been reported. We report 5-year efficacy and safety outcomes phase III KEYNOTE-407 study (ClinicalTrials.gov identifier: NCT02775435 ). Eligible patients with previously untreated, metastatic squamous non–small-cell lung cancer (NSCLC) were randomly assigned 1:1 pembrolizumab 200 mg placebo plus carboplatin paclitaxel/nab-paclitaxel once every 3 weeks four cycles, followed by up 35 cycles. Primary overall survival (OS) progression-free (PFS) per RECIST version 1.1 blinded independent central review (BICR). Five hundred fifty-nine intention-to-treat population (pembrolizumab chemotherapy, n = 278; 281). median time random assignment data cutoff was 56.9 (range, 49.9-66.2) months. OS PFS improved chemotherapy versus (hazard ratio [95% CI], 0.71 [0.59 0.85] 0.62 [0.52 0.74]), rates of 18.4% 9.7%, respectively. Toxicity manageable. Among 55 who completed cycles pembrolizumab, objective response rate 90.9% 3-year after completion (approximately 5 years assignment) 69.5%. Pembrolizumab maintained benefit NSCLC is a standard-of-care first-line treatment option regardless programmed death ligand 1 expression.

Language: Английский

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Neoadjuvant immune checkpoint blockade: A window of opportunity to advance cancer immunotherapy

Cancer Cell, Journal Year: 2023, Volume and Issue: 41(9), P. 1551 - 1566

Published: Aug. 17, 2023

Language: Английский

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Phase III, Randomized Study of Atezolizumab Plus Bevacizumab and Chemotherapy in Patients With EGFR- or ALK-Rearranged or Translocated Non–Small-Cell Lung Cancer (ATTLAS, KCSG-LU19-04)

Journal of Clinical Oncology, Journal Year: 2023, Volume and Issue: 42(11), P. 1241 - 1251

Published: Oct. 20, 2023

PURPOSE In the treatment of non–small-cell lung cancer (NSCLC) with a driver mutation, role anti–PD-(L)1 antibody after tyrosine kinase inhibitor (TKI) remains unclear. This randomized, open-label, multicenter, phase III study evaluates efficacy atezolizumab plus bevacizumab, paclitaxel, and carboplatin (ABCP ) in EGFR- or ALK-rearranged translocated NSCLC upon progression on TKI therapy. MATERIALS AND METHODS We compared clinical ABCP followed by maintenance therapy bevacizumab pemetrexed cisplatin (PC) maintenance. The primary end point was progression-free survival (PFS). RESULTS A total 228 patients activating EGFR mutation (n = 215) ALK translocation 13) were enrolled from 16 sites Republic Korea randomly assigned at 2:1 ratio to either 154) PC arm 74). median follow-up duration 26.1 months (95% CI, 24.7 28.2). Objective response rates (69.5% v 41.9%, P < .001) PFS (8.48 5.62 months, hazard [HR], 0.62 [95% 0.45 0.86]; .004) significantly better than arm. benefit increased as PD-L1 expression increased, an HR 0.47, 0.41, 0.24 for ≥1%, ≥10%, ≥50%, respectively. Overall similar between (20.63 20.27 HR, 1.01 0.69 1.46]; .975). safety profile comparable that previously reported, no additional signals, but higher treatment-related adverse events observed CONCLUSION To our knowledge, this is first randomized demonstrate anti–PD-L1 combination chemotherapy who have progressed relevant targeted

Language: Английский

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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

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Cold and hot tumors: from molecular mechanisms to targeted therapy

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Oct. 18, 2024

Immunotherapy has made significant strides in cancer treatment, particularly through immune checkpoint blockade (ICB), which shown notable clinical benefits across various tumor types. Despite the transformative impact of ICB treatment therapy, only a minority patients exhibit positive response to it. In with solid tumors, those who respond well typically demonstrate an active profile referred as "hot" (immune-inflamed) phenotype. On other hand, non-responsive may distinct "cold" (immune-desert) phenotype, differing from features tumors. Additionally, there is more nuanced "excluded" positioned between and categories, known type. Effective differentiation understanding intrinsic factors, characteristics, TME, external factors are critical for predicting results. It widely accepted that therapy exerts profound effect on limited efficacy against or "altered" necessitating combinations therapeutic modalities enhance cell infiltration into tissue convert tumors ones. Therefore, aligning traits this review systematically delineates respective influencing extensively discusses varied approaches drug targets based assess efficacy.

Language: 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, Journal Year: 2024, Volume and Issue: 12(2), P. e008189 - e008189

Published: Feb. 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.

Language: Английский

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Therapy for Stage IV Non–Small Cell Lung Cancer Without Driver Alterations: ASCO Living Guideline, Version 2023.3

Journal of Clinical Oncology, Journal Year: 2024, Volume and Issue: 42(11), P. e23 - e43

Published: Feb. 28, 2024

Living guidelines are developed for selected topic areas with rapidly evolving evidence that drives frequent change in recommended clinical practice. updated on a regular schedule by standing expert panel systematically reviews the health literature continuous basis, as described ASCO Guidelines Methodology Manual . follow Conflict of Interest Policy Implementation Clinical Practice and updates not intended to substitute independent professional judgment treating provider do account individual variation among patients. See complete disclaimer Appendix 1 2 more. Updates published regularly can be found at https://ascopubs.org/nsclc-non-da-living-guideline PURPOSE To provide evidence-based recommendations patients stage IV non–small cell lung cancer (NSCLC) without driver alterations. METHODS This living guideline offers continually based an ongoing systematic review randomized trials (RCTs), latest time frame spanning February October 2023. An Expert Panel medical oncology, pulmonary, community research methodology, advocacy experts were convened. The search included reviews, meta-analyses, controlled trials. Outcomes interest include efficacy safety. members used available informal consensus develop recommendations. RESULTS consolidates all previous reflects body informing this topic. Ten new RCTs identified date. RECOMMENDATIONS Evidence-based address first, second, subsequent treatment options Additional information is www.asco.org/living-guidelines

Language: Английский

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CXCL9/10-engineered dendritic cells promote T cell activation and enhance immune checkpoint blockade for lung cancer

Cell Reports Medicine, Journal Year: 2024, Volume and Issue: 5(4), P. 101479 - 101479

Published: March 21, 2024

Immune checkpoint blockade (ICB) with PD-1/PD-L1 inhibition has revolutionized the treatment of non-small cell lung cancer (NSCLC). Durable responses, however, are observed only in a subpopulation patients. Defective antigen presentation and an immunosuppressive tumor microenvironment (TME) can lead to deficient T recruitment ICB resistance. We evaluate intratumoral (IT) vaccination CXCL9- CXCL10-engineered dendritic cells (CXCL9/10-DC) as strategy overcome IT CXCL9/10-DC leads enhanced infiltration activation TME murine NSCLC models. The antitumor efficacy is dependent on CD4+ CD8+ cells, well CXCR3-dependent trafficking from lymph node. CXCL9/10-DC, combination ICB, overcomes resistance establishes systemic tumor-specific immunity These studies provide mechanistic understanding CXCL9/10-DC-mediated host immune support clinical translation augment NSCLC.

Language: 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, Journal Year: 2024, Volume and Issue: 19(8), P. 1228 - 1241

Published: April 18, 2024

Language: Английский

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