Pembrolizumab Plus Pemetrexed and Platinum in Nonsquamous Non–Small-Cell Lung Cancer: 5-Year Outcomes From the Phase 3 KEYNOTE-189 Study

Journal of Clinical Oncology, Journal Year: 2023, Volume and Issue: 41(11), P. 1992 - 1998

Published: Feb. 21, 2023

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically on the based 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 present 5-year outcomes phase 3 KEYNOTE-189 study (ClinicalTrials.gov identifier: NCT02578680 ). Eligible patients with previously untreated metastatic nonsquamous non–small-cell lung cancer without EGFR/ALK alterations were randomly assigned 2:1 pembrolizumab 200 mg placebo once every weeks up 35 cycles pemetrexed and investigator's choice of carboplatin/cisplatin four cycles, followed by maintenance until disease progression unacceptable toxicity. Primary overall survival (OS) progression-free (PFS). Among 616 (n = 410, plus pemetrexed-platinum; n 206, pemetrexed-platinum), median time random assignment data cutoff (March 8, 2022) was 64.6 (range, 60.1-72.4) months. Hazard ratio (95% CI) OS 0.60 (0.50 0.72) PFS 0.50 (0.42 0.60) platinum-pemetrexed versus platinum-pemetrexed. rates 19.4% 11.3%. Toxicity manageable. 57 who completed pembrolizumab, objective response rate 86.0% 3-year after completing (approximately 5 years assignment) 71.9%. Pembrolizumab pemetrexed-platinum maintained benefits pemetrexed-platinum, regardless programmed cell death ligand-1 expression. These continue support as a standard care alterations.

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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Four-year overall survival update from the phase III HIMALAYA study of tremelimumab plus durvalumab in unresectable hepatocellular carcinoma

Annals of Oncology, Journal Year: 2024, Volume and Issue: 35(5), P. 448 - 457

Published: Feb. 19, 2024

BackgroundIn the phase III HIMALAYA study (NCT03298451) in unresectable hepatocellular carcinoma (uHCC), STRIDE (Single Tremelimumab Regular Interval Durvalumab) significantly improved overall survival (OS) versus sorafenib; durvalumab monotherapy was noninferior to sorafenib for OS. Results reported herein are from a four-year updated OS analysis of HIMALAYA.Patients and methodsParticipants with uHCC no previous systemic treatment were randomized (n=393), (n=389), or (n=389). The data cut-off January 23, 2023. serious adverse events (AEs) assessed. Additionally, baseline characteristics subsequent therapies analyzed long-term survivors (≥36 months beyond randomization).ResultsFor STRIDE, durvalumab, sorafenib, median (95% CI) follow-up 49.12 (46.95-50.17), 48.46 (46.82-49.81), 47.31 (45.08-49.15) months, respectively. HR 0.78 (0.67-0.92). 36-month rate 30.7% 19.8% sorafenib. 48-month remained higher at 25.2%, 15.1% benefit observed across clinically relevant subgroups further participants who achieved disease control. Long-term (n=103) included subgroups, 57.3% (59/103) had anticancer therapy. No new treatment-related AEs occurred primary (17.5%; 68/388). Durvalumab maintained noninferiority late onset safety signals identified.ConclusionsThese represent longest date studies uHCC. unprecedented three- rates reinforce sustained tolerable yet differentiated profile other current therapies. continue support benefits diverse population, reflective globally.

Language: Английский

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Immune-checkpoint inhibition for resectable non-small-cell lung cancer — opportunities and challenges

Nature Reviews Clinical Oncology, Journal Year: 2023, Volume and Issue: 20(10), P. 664 - 677

Published: July 24, 2023

Language: Английский

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Defining clinically useful biomarkers of immune checkpoint inhibitors in solid tumours

Nature reviews. Cancer, Journal Year: 2024, Volume and Issue: 24(7), P. 498 - 512

Published: June 12, 2024

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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HDAC-targeting epigenetic modulators for cancer immunotherapy

European Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 265, P. 116129 - 116129

Published: Jan. 5, 2024

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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Immune checkpoint inhibitors: breakthroughs in cancer treatment

Cancer Biology and Medicine, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 11

Published: May 24, 2024

Over the past two decades, immunotherapies have increasingly been considered as first-line treatments for most cancers. One such treatment is immune checkpoint blockade (ICB), which has demonstrated promising results against various solid tumors in clinical trials. Monoclonal antibodies (mAbs) are currently available inhibitors (ICIs). These ICIs target specific checkpoints, including cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and programmed cell death protein 1 (PD-1). Clinical trial strongly support feasibility of this immunotherapeutic approach. However, a substantial proportion patients with cancer develop resistance or tolerance to treatment, owing tumor evasion mechanisms that counteract host response. Consequently, research focus aimed at identifying additional synergistic inhibitory receptors enhance effectiveness anti-PD-1, anti-programmed ligand (anti-PD-L1), anti-CTLA-4 treatments. Recently, several molecular targets identified, T immunoreceptor Ig ITIM domains (TIGIT), mucin domain containing-3 (TIM-3), lymphocyte activation gene-3 (LAG-3), V-domain immunoglobulin suppressor (VISTA), B attenuator (BTLA), signal-regulatory α (SIRPα). Functional mAbs targeting these molecules under development. CTLA-4, PD-1/PD-L1, other recently discovered proteins distinct structures forefront research. This review discusses structures, well progress their potential applications.

Language: Английский

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Immunotherapy or Chemoimmunotherapy in Older Adults With Advanced Non–Small Cell Lung Cancer

JAMA Oncology, Journal Year: 2024, Volume and Issue: 10(4), P. 439 - 439

Published: March 7, 2024

Immune checkpoint inhibitor (ICI) plus chemotherapy combination treatment (ICI-chemotherapy) is now a standard for non-small cell lung cancer (NSCLC) without targetable oncogene alterations, but there are few data on ICI-chemotherapy patients 75 years and older.

Language: Английский

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