Advancements in fourth-generation EGFR TKIs in EGFR-mutant NSCLC: Bridging biological insights and therapeutic development.

Third-generation EGFR tyrosine kinase inhibitor (TKIs) have revolutionized the treatment landscape for patients with non-small cell lung cancer (NSCLC) harboring EGFR activating mutations, with improved long-term outcomes compared to first-generation TKIs. Nevertheless, disease progression inevitably occurs, limiting osimertinib long-term efficacy. Indeed, the molecular biology underlying acquired resistance to first-line osimertinib is multifaceted and includes the emergence of on-target and off-target alterations.

Management of Non-Metastatic Non-Small Cell Lung Cancer (NSCLC) with Driver Gene Alterations: An Evolving Scenario.

The ever-growing knowledge regarding NSCLC molecular biology has brought innovative therapies into clinical practice; however, the treatment situation in the non-metastatic setting is rapidly evolving. Indeed, immunotherapy-based perioperative treatments are currently considered the standard of care for patients with resectable NSCLC in the absence of mutations or gene rearrangements. Recently, data have been presented on the use of tyrosine kinase inhibitors (TKIs) in the adjuvant and locally advanced setting for patients with NSCLC harboring such driver gene alterations.

Non-Small-Cell Lung Cancers (NSCLCs) Harboring RET Gene Fusion, from Their Discovery to the Advent of New Selective Potent RET Inhibitors: "Shadows and Fogs".

RET fusions are relatively rare in Non-Small-Cell Lung Cancers (NSCLCs), being around 1-2% of all NSCLCs. They share the same clinical features as the other fusion-driven NSCLC patients, as follows: younger age, adenocarcinoma histology, low exposure to tobacco, and high risk of spreading to the brain. Chemotherapy and immunotherapy have a low impact on the prognosis of these patients.

Co-Occurring Driver Genomic Alterations in Advanced Non-Small-Cell Lung Cancer (NSCLC): A Retrospective Analysis.

Actionable driver mutations account for 40-50% of NSCLC cases, and their identification clearly affects treatment choices and outcomes. Conversely, non-actionable mutations are genetic alterations that do not currently have established treatment implications. Among co-occurring alterations, the identification of concurrent actionable genomic alterations is a rare event, potentially impacting prognosis and treatment outcomes.

Post-Progression Analysis of -Mutant NSCLC Following Osimertinib Therapy in Real-World Settings.

Background: Platinum-based chemotherapy is the current standard treatment option in patients with -mutant non-small-cell lung cancer (NSCLC) who progress on osimertinib. However, outcomes with chemotherapy are dismal, and the treatment of central nervous system (CNS) disease is an unmet need in this setting.

Methods: Patients with -mutant NSCLC who were candidates to receive osimertinib in the metastatic setting at our Center from 2015 to 2022 were retrospectively evaluated to identify patients who received standard platinum-based chemotherapy post-osimertinib.

New Generations of Tyrosine Kinase Inhibitors in Treating NSCLC with Oncogene Addiction: Strengths and Limitations.

Tyrosine kinase inhibitors (TKIs) revolutionized the treatment of patients with advanced or metastatic non-small cell lung cancer (NSCLC) harboring most driver gene alterations. Starting from the first generation, research rapidly moved to the development of newer, more selective generations of TKIs, obtaining improved results in terms of disease control and survival. However, the use of novel generations of TKIs is not without limitations.

MET in Non-Small-Cell Lung Cancer (NSCLC): Cross 'a Long and Winding Road' Looking for a Target.

Non-Small-Cell Lung Cancer (NSCLC) can harbour different MET alterations, such as MET overexpression (MET OE), MET gene amplification (MET AMP), or MET gene mutations. Retrospective studies of surgical series of patients with MET-dysregulated NSCLC have shown worse clinical outcomes irrespective of the type of specific MET gene alteration. On the other hand, earlier attempts failed to identify the 'druggable' molecular gene driver until the discovery of MET exon 14 skipping mutations (METex14).

Association between Contrast-Enhanced Computed Tomography Radiomic Features, Genomic Alterations and Prognosis in Advanced Lung Adenocarcinoma Patients.

Non-invasive methods to assess mutational status, as well as novel prognostic biomarkers, are warranted to foster therapy personalization of patients with advanced non-small cell lung cancer (NSCLC). This study investigated the association of contrast-enhanced Computed Tomography (CT) radiomic features of lung adenocarcinoma lesions, alone or integrated with clinical parameters, with tumor mutational status (, , alterations) and Overall Survival (OS). In total, 261 retrospective and 48 prospective patients were enrolled.

Immune checkpoint inhibitors in EGFR-mutant non-small cell lung cancer: A systematic review.

Background: Since their first introduction in clinical practice, immune checkpoint inhibitors showed limited benefit in patients with NSCLC harboring EGFR mutations. With the rationale of increasing immune activation, combinatorial ICI strategies have been evaluated also in this subgroup of patients.

Methods: We performed a systematic review on efficacy of ICI-based strategies in EGFR-mutant NSCLC according to most updated evidence.

Sustained Improvement in the Management of Patients with Non-Small-Cell Lung Cancer (NSCLC) Harboring ALK Translocation: Where Are We Running?

ALK translocation amounts to around 3-7% of all NSCLCs. The clinical features of ALK+ NSCLC are an adenocarcinoma histology, younger age, limited smoking history, and brain metastases. The activity of chemotherapy and immunotherapy is modest in ALK+ disease.

Comparison of real-world data (RWD) analysis on efficacy and post-progression outcomes with pembrolizumab plus chemo vs chemo alone in metastatic non-squamous non-small cell lung cancer with PD-L1 < 50.

Background: Following the introduction of immunotherapy (IO) in the first-line (1L) treatment in patients with non-small cell lung cancer (NSCLC) without sensitizing EGFR/ALK mutations, increasing real-world data depict how difficult it is to replicate data from clinical trials to clinical practice, with high rates of early treatment failure. In the context of chemo-IO, our study aims to compare platinum-pemetrexed-pembrolizumab combination to platinum-doublet alone in patients with low PD-L1 (<50%).

Methods: We retrospectively collected medical records from patients with stage IV non-squamous NSCLC with PD-L1<50%, consecutively treated at our Centre from 2016 to 2021.

Association between changes in thioredoxin reductase and other peripheral blood biomarkers with response to PD-1 inhibitor-based combination immunotherapy in non-small cell lung cancer: a retrospective study.

Background: Immunotherapy deeply changed the treatment paradigm of advanced non-small cell lung cancer (NSCLC) in the past years. However, the objective response rate (ORR) after immunotherapy is about 20-30% of NSCLC patients. Therefore, identification of predictive biomarkers is crucial for selecting patients with NSCLC who would most benefit from programmed cell death receptor protein 1 (PD-1) inhibitor-based immunotherapy.

The new era of immune checkpoint inhibition and target therapy in early-stage non-small cell lung cancer. A review of the literature.

Surgery is the best option for patients with early stage non-small cell lung cancer (NSCLC). However, the rate of local and metastatic recurrences following surgery alone is high, especially in NSCLC patients with N2 lymph node involvement. A recent American study showed that 60% of lung cancers are diagnosed in an advanced stage, and less than 20% are diagnosed in an early, resectable stage.

Fears and Perception of the Impact of COVID-19 on Patients With Lung Cancer: A Mono-Institutional Survey.

In February 2020, Italy became one of the first countries to be plagued by the SARS-CoV-2 pandemic, COVID-19. In March 2020, the Italian government decreed a lockdown for the whole country, which overturned communication systems, hospital organization, and access to patients and their relatives and carers. This issue had a particular regard for cancer patients.

Interstitial pneumonitis in the COVID-19 era: a difficult differential diagnosis in patients with lung cancer.

In this coronavirus 2019 (COVID-19) era, when pneumonitis occurs in patients with lung cancer receiving immune checkpoint inhibitors (ICIs), a major challenge is to make a rapid and correct differential diagnosis among drug-induced pulmonary toxicity, tumour progression, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced pneumonitis. While waiting for polymerase chain reaction (PCR) testing results, an accurate evaluation of the symptoms and serologic features can help us make a first diagnostic hypothesis and quickly start correct treatment. Physicians need a collaborative effort to develop and share a common database reporting clinical (anosmia, dysgeusia), serologic, and radiologic data in ICI-treated patients with lung cancer developing interstitial disease to create an evidence-based clinical diagnostic algorithm.

Clinical features affecting survival in metastatic NSCLC treated with immunotherapy: A critical review of published data.

Immune checkpoint inhibitors (ICIs) represent one of the main steps forward for the treatment of advanced or metastatic non-small-cell lung cancer (NSCLC), without oncogenic driver alterations. Despite this recent progress, only a minority of patients achieve a broad and durable benefit and another proportion report poor survival and sometimes fast disease progression, confirming the need to optimise the patient's selection. To date, several issues are unsolved about how to personalise the immunotherapy treatment for individual patients.

Results of Multilevel Containment Measures to Better Protect Lung Cancer Patients From COVID-19: The IEO Model.

A novel coronavirus causing severe acute respiratory syndrome (SARS), named SARS-CoV-2, was identified at the end of 2019. The spread of coronavirus disease 2019 (COVID-19) has progressively expanded from China, involving several countries throughout the world, leading to the classification of the disease as a pandemic by the World Health Organization (WHO). According to published reports, COVID-19 severity and mortality are higher in elderly patients and those with active comorbidities.

Efficacy of Anti-PD1/PD-L1 Therapy (IO) in KRAS Mutant Non-small Cell Lung Cancer Patients: A Retrospective Analysis.

Background/aim: The role of anti-PD1/PD-L1 therapy (IO) in NSCLC harboring driver mutations is questionable. This study aimed to examine the efficacy of IO in patients with non-small cell lung cancer (NSCLC) with a KRAS mutation (KRAS).

Patients And Methods: We retrospectively identified NSCLC patients harboring KRAS mutation treated with IO in our Institution.

ROS1-rearranged Non-small-cell Lung Cancer is Associated With a High Rate of Venous Thromboembolism: Analysis From a Phase II, Prospective, Multicenter, Two-arms Trial (METROS).

Background: Patients with cancer are at increased risk for venous thromboembolism (VTE), and 8% to 15% of patients with advanced non-small-cell lung cancer (NSCLC) experience a VTE event during the course of their disease. The incidence of VTE in molecularly defined NSCLC subgroups is still unclear. In this study, we investigated the incidence and the clinical correlates of VTE in patients with ROS1-rearranged NSCLC enrolled in the METROS trial (NCT02499614).