Lung cancer

The Lancet, Journal Year: 2021, Volume and Issue: 398(10299), P. 535 - 554

Published: July 21, 2021

Language: Английский

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Top 10 Challenges in Cancer Immunotherapy

Immunity, Journal Year: 2020, Volume and Issue: 52(1), P. 17 - 35

Published: Jan. 1, 2020

Language: Английский

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Atezolizumab for First-Line Treatment of PD-L1–Selected Patients with NSCLC

New England Journal of Medicine, Journal Year: 2020, Volume and Issue: 383(14), P. 1328 - 1339

Published: Sept. 30, 2020

The efficacy and safety of the anti-programmed death ligand 1 (PD-L1) monoclonal antibody atezolizumab, as compared with those platinum-based chemotherapy, first-line treatment for patients metastatic non-small-cell lung cancer (NSCLC) PD-L1 expression are not known.We conducted a randomized, open-label, phase 3 trial involving nonsquamous or squamous NSCLC who had previously received chemotherapy on at least 1% tumor cells tumor-infiltrating immune assessed by SP142 immunohistochemical assay. Patients were assigned in 1:1 ratio to receive atezolizumab chemotherapy. Overall survival (primary end point) was tested hierarchically according status among intention-to-treat population whose tumors wild-type respect EGFR mutations ALK translocations. Within tumors, overall progression-free also prospectively subgroups defined findings two assays well blood-based mutational burden.Overall, 572 enrolled. In subgroup highest (205 patients), median longer 7.1 months group than (20.2 vs. 13.1 months; hazard death, 0.59; P = 0.01). Among all could be evaluated safety, adverse events occurred 90.2% 94.7% group; grade 4 30.1% 52.5% respective groups. favored high burden.Atezolizumab resulted significantly expression, regardless histologic type. (Funded F. Hoffmann-La Roche/Genentech; IMpower110 ClinicalTrials.gov number, NCT02409342.).

Language: Английский

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Review of Indications of FDA-Approved Immune Checkpoint Inhibitors per NCCN Guidelines with the Level of Evidence

Cancers, Journal Year: 2020, Volume and Issue: 12(3), P. 738 - 738

Published: March 20, 2020

Cancer is associated with higher morbidity and mortality the second leading cause of death in US. Further, some nations, cancer has overtaken heart disease as mortality. Identification molecular mechanisms by which cancerous cells evade T cell-mediated cytotoxic damage led to modern era immunotherapy treatment. Agents that release these immune brakes have shown activity recover dysfunctional regress various cancer. Both T-lymphocyte-associated protein 4 (CTLA-4) Programmed Death-1 (PD-1) play their role physiologic on unrestrained effector function. CTLA-4 (CD 152) a B7/CD28 family; it mediates immunosuppression indirectly diminishing signaling through co-stimulatory receptor CD28. Ipilimumab first only FDA-approved inhibitor; PD-1 an inhibitory transmembrane expressed cells, B Natural Killer (NKs), Myeloid-Derived Suppressor Cells (MDSCs). Death-Ligand 1 (PD-L1) surface multiple tissue types, including many tumor hematopoietic cells. PD-L2 more restricted Blockade /PDL-1 pathway can enhance anti-tumor cell reactivity promotes control over Since FDA approval ipilimumab (human IgG1 k anti-CTLA-4 monoclonal antibody) 2011, six checkpoint inhibitors (ICIs) been approved for therapy. nivolumab, pembrolizumab, cemiplimab PD-L1 atezolizumab, avelumab, durvalumab are current list agents addition ipilimumab. In this review paper, we discuss each inhibitor (ICI), landmark trials approval, strength evidence per National Comprehensive Network (NCCN), broadly utilized medical oncologists hematologists daily practice.

Language: Английский

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Ferroptosis, necroptosis, and pyroptosis in anticancer immunity

Journal of Hematology & Oncology, Journal Year: 2020, Volume and Issue: 13(1)

Published: Aug. 10, 2020

Abstract In recent years, cancer immunotherapy based on immune checkpoint inhibitors (ICIs) has achieved considerable success in the clinic. However, ICIs are significantly limited by fact that only one third of patients with most types respond to these agents. The induction cell death mechanisms other than apoptosis gradually emerged as a new treatment strategy because tumors harbor innate resistance apoptosis. date, possibility combining two modalities not been discussed systematically. Recently, few studies revealed crosstalk between distinct and antitumor immunity. pyroptosis, ferroptosis, necroptosis combined showed synergistically enhanced activity, even ICI-resistant tumors. Immunotherapy-activated CD8+ T cells traditionally believed induce tumor via following main pathways: (i) perforin-granzyme (ii) Fas-FasL. identified mechanism which suppress growth inducing ferroptosis provoked review relationship system activation. Hence, this review, we summarize knowledge reciprocal interaction immunity mechanisms, particularly necroptosis, three potentially novel immunogenic death. Because evidence is derived from using animal models, also reviewed related bioinformatics data available for human tissues public databases, partially confirmed presence interactions activation

Language: Английский

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NCCN Guidelines Insights: Non–Small Cell Lung Cancer, Version 1.2020

Journal of the National Comprehensive Cancer Network, Journal Year: 2019, Volume and Issue: 17(12), P. 1464 - 1472

Published: Dec. 1, 2019

The NCCN Guidelines for Non-Small Cell Lung Cancer (NSCLC) address all aspects of management NSCLC. These Insights focus on recent updates in immunotherapy. For the 2020 update, systemic therapy regimens have been categorized using a new preference stratification system; certain are now recommended as "preferred interventions," whereas others either "other interventions" or "useful under circumstances."

Language: Английский

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Updated Analysis From KEYNOTE-189: Pembrolizumab or Placebo Plus Pemetrexed and Platinum for Previously Untreated Metastatic Nonsquamous Non–Small-Cell Lung Cancer

Journal of Clinical Oncology, Journal Year: 2020, Volume and Issue: 38(14), P. 1505 - 1517

Published: March 9, 2020

In KEYNOTE-189, first-line pembrolizumab plus pemetrexed-platinum significantly improved overall survival (OS) and progression-free (PFS) compared with placebo in patients metastatic nonsquamous non‒small-cell lung cancer (NSCLC), irrespective of tumor programmed death-ligand 1 (PD-L1) expression. We report an updated analysis from KEYNOTE-189 (ClinicalTrials.gov: NCT02578680).Patients were randomly assigned (2:1) to receive pemetrexed platinum (n = 410) or 206) every 3 weeks for 4 cycles, then maintenance up a total 35 cycles. Eligible disease progression the placebo-combination group could cross over monotherapy. Response was assessed per RECIST (version 1.1) by central review. No alpha this analysis.As September 21, 2018 (median follow-up, 23.1 months), median (95% CI) OS 22.0 (19.5 25.2) months pembrolizumab-combination versus 10.7 (8.7 13.6) (hazard ratio [HR], 0.56; 95% CI, 0.45 0.70]). Median PFS 9.0 (8.1 9.9) 4.9 (4.7 5.5) months, respectively (HR, 0.48; 0.40 0.58). time randomization objective on next-line treatment death any cause, whichever occurred first (progression-free-survival-2; PFS-2) 17.0 (15.1 19.4) (7.6 10.4) 0.49; 0.59). benefits observed regardless PD-L1 expression presence liver/brain metastases. Incidence grade 3-5 adverse events similar (71.9%) (66.8%) groups.First-line continued demonstrate substantially NSCLC, metastases, manageable safety tolerability.

Language: Английский

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Toward personalized treatment approaches for non-small-cell lung cancer

Nature Medicine, Journal Year: 2021, Volume and Issue: 27(8), P. 1345 - 1356

Published: Aug. 1, 2021

Language: Английский

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Liver metastasis restrains immunotherapy efficacy via macrophage-mediated T cell elimination

Nature Medicine, Journal Year: 2021, Volume and Issue: 27(1), P. 152 - 164

Published: Jan. 1, 2021

Language: Английский

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First-Line Immunotherapy for Non–Small-Cell Lung Cancer

Journal of Clinical Oncology, Journal Year: 2022, Volume and Issue: 40(6), P. 586 - 597

Published: Jan. 5, 2022

For patients with metastatic non-small-cell lung cancer (mNSCLC), the last decade has been characterized by critical progress that contributed to substantially improved survival. In particular, development of specific antibodies against programmed death (PD-1) receptor, death-ligand 1 (PD-L1), and cytotoxic T-lymphocyte-associated protein 4 receptor in therapeutic strategy mNSCLC either first- or second-line settings have led unprecedented prolonged survival for a proportion these patients. Although clinical immune checkpoint inhibitors anti-PD-1 PD-L1 therapies largely began as monotherapy setting, more recent shifted toward combination approaches first-line well integration immunotherapy into paradigm earlier stages. Today, exception harboring targetable oncogenes, nearly all receive PD-1 therapy settings. Here we report current status together challenges selecting best immunotherapeutic approach individual patient.

Language: Английский

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