Complications following novel therapies for non‐small cell lung cancer

Skribek, Marcus; Rounis, Konstantinos; Tsakonas, Georgios; Ekman, Simon

doi:10.1111/joim.13445

Cited by 16 publications

(7 citation statements)

References 150 publications

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“…However, even these low doses did result in subsequent ALT increase, leading to the decision to switch within the drug class to entrectinib. Even though hepatotoxicity is a typical adverse event of both drugs and known class effect, as with other TKIs such as ALK-, EGFR-, or MET inhibitor treatment, tolerability with another drug within the same drug class sometimes can be better and is therefore the preferred option before abandoning targeted therapy in oncogene-addicted NSCLC [27][28][29][30][31].…”

Section: Case Reports In Oncologymentioning

confidence: 99%

Complete Response on Larotrectinib in NTRK2 Fusion-Positive Non-Small Cell Lung Cancer

Frehner,

Haefliger,

Cerciello

et al. 2023

Case Rep Oncol

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In patients with non-small cell lung cancer (NSCLC) harboring a fusion of the neurotrophic receptor kinase (NTRK) gene 1 or 3, treatment with tropomyosin kinase (TRK) inhibitors have shown promising results, however so far no data on efficacy of these agents in patients with NSCLC and NTRK2 fusion are available. We present a case of a female patient with NTRK2-positive NSCLC with a complete ongoing response on therapy with larotrectinib, suggesting efficacy of first-generation TRK inhibitors also in NTRK2-positive NSCLC.

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Section: Case Reports In Oncologymentioning

confidence: 99%

Complete Response on Larotrectinib in NTRK2 Fusion-Positive Non-Small Cell Lung Cancer

Frehner,

Haefliger,

Cerciello

et al. 2023

Case Rep Oncol

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“…Recently, immune checkpoint inhibitor (ICI)‐based immunotherapy that enhances T‐cell activation to eliminate cancer cells has become an indispensable second‐line therapy for NSCLC patients with innate and required resistance to TKIs, and as first‐line therapy for those lacking targetable driver mutations 4–6 . With these recent additions to the treatment landscape of NSCLC, the 5‐year overall survival (OS) for patients with metastatic disease has improved from below 5% to more than 30% with TKIs, and 20% for ICIs 7–9 . Accurate identification of patients with poor prognosis that require aggressive treatment could guide treatment selection and further improve the outcomes of NSCLC patients.…”

Section: Introductionmentioning

confidence: 99%

“… 4 , 5 , 6 With these recent additions to the treatment landscape of NSCLC, the 5‐year overall survival (OS) for patients with metastatic disease has improved from below 5% to more than 30% with TKIs, and 20% for ICIs. 7 , 8 , 9 Accurate identification of patients with poor prognosis that require aggressive treatment could guide treatment selection and further improve the outcomes of NSCLC patients.…”

Section: Introductionmentioning

confidence: 99%

Identification of age‐ and immune‐related gene signatures for clinical outcome prediction in lung adenocarcinoma

et al. 2023

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BackgroundThe understanding of the factors causing decreased overall survival (OS) in older patients compared to younger patients in lung adenocarcinoma (LUAD) remains.MethodsGene expression profiles of LUAD were obtained from publicly available databases by Kaplan‐Meier analysis was performed to determine whether age was associated with patient OS. The immune cell composition in the tumor microenvironment (TME) was evaluated using CIBERSORT. The fraction of stromal and immune cells in tumor samples were also using assessed using multiple tools including ESTIMATE, EPIC, and TIMER. Differentially expressed genes (DEGs) from the RNA‐Seq data that were associated with age and immune cell composition were identified using the R package DEGseq. A 22‐gene signature composed of DEGs associated with age and immune cell composition that predicted OS were constructed using Least Absolute Shrinkage and Selection Operator (LASSO).ResultsIn The Cancer Genome Atlas (TCGA)‐LUAD dataset, we found that younger patients (≤70) had a significant better OS compared to older patients (>70). In addition, older patients had significantly higher expression of immune checkpoint proteins including inhibitory T cell receptors and their ligands. Moreover, analyses using multiple bioinformatics tools showed increased immune infiltration, including CD4+ T cells, in older patients compared to younger patients. We identified a panel of genes differentially expressed between patients >70 years compared to those ≤70 years, as well as between patients with high or low immune scores and selected 84 common genes to construct a prognostic gene signature. A risk score calculated based on 22 genes selected by LASSO predicted 1, 3, and 5‐year OS, with an area under the curve (AUC) of 0.72, 0.72, 0.69, receptively, in TCGA‐LUAD dataset and an independent validation dataset available from the European Genome‐phenome Archive (EGA).ConclusionOur results demonstrate that age contributes to OS of LUAD patients atleast in part through its association with immune infiltration in the TME.

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“…As with other drug-induced adverse events, ICI-related pneumonitis is a diagnosis of exclusion, which implies that alternative diagnoses, mainly infection and recurrence/progression of cancer, need to be excluded [ 8 ▪ ]. Most irAEs are mild to moderate in severity, although severe and even fatal events have also been reported [ 1 , 9 ], and occur idiosyncratically, generally within weeks to 3 months after treatment initiation, but they can also appear as late as 1 year after treatment termination [ 10 ▪ ]. Overall, ICIs present a favorable benefit-to-risk profile compared to conventional chemotherapy, with PD-L1 inhibitors being less toxic than PD-1 inhibitors (probably because they do not block the PD-L2 and PD-1 interaction), and high-grade toxicity being more common with CTLA-4/PD-1 or PD-L1 combination than with anti-PD-1 monotherapy.…”

Section: Introductionmentioning

confidence: 99%

Pulmonary adverse events following immune checkpoint inhibitors

Spagnolo

Chaudhuri

Bernardinello

et al. 2022

Current Opinion in Pulmonary Medicine

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Purpose of reviewImmune checkpoint inhibitors (ICIs) have rapidly become a mainstay of cancer treatment. However, immune modulation resulting from checkpoint inhibition can cause inflammation in any organ system, with pneumonitis being one of the most severe immune-related adverse events (irAEs). Here, we review the most recent literature on pulmonary adverse events following ICIs.Recent findingsSeveral systematic reviews and meta-analyses of data from trials of antiprogrammed death-1 (PD-1; nivolumab, pembrolizumab), anti-PD-ligand-1 (PD-L1; atezolizumab, avelumab, durvalumab) and anticytotoxic T lymphocyte antigen-4 (CTLA-4; ipilimumab or tremelimumab) in patients with advanced cancer have explored the relative risk and incidence of lung toxicity among different tumor types and therapeutic regimens. They have showed that the incidence of all-grade (1–4) and high-grade (3–4) pneumonitis is significantly higher in nonsmall cell lung cancer (NSCLC) compared with other tumor types. In addition, they have demonstrated that immunotherapy, especially monoimmunotherapy, has a significantly lower risk of irAEs compared to immune-chemotherapy. Treatment for lung cancer, preexisting interstitial lung disease, smoking history and male sex appear to increase the risk for ICI-related pneumonitis.SummaryLung toxicity is an uncommon but potentially severe and even fatal complication of ICIs. Timely recognition is critically important but challenging, particularly in patients with lung cancer wherein drug toxicity can mimic disease progression or recurrence.

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Complications following novel therapies for non‐small cell lung cancer

Cited by 16 publications

References 150 publications

Complete Response on Larotrectinib in NTRK2 Fusion-Positive Non-Small Cell Lung Cancer

Complete Response on Larotrectinib in NTRK2 Fusion-Positive Non-Small Cell Lung Cancer

Identification of age‐ and immune‐related gene signatures for clinical outcome prediction in lung adenocarcinoma

Pulmonary adverse events following immune checkpoint inhibitors

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