Publications by authors named "Gridelli Cesare"

Objective: ALK, ROS1, NTRK, and RET gene fusions and MET exon 14 skipping alterations represent fundamental predictive biomarkers for advanced non-small cell lung cancer (NSCLC) patients to ensure the best treatment choice. In this scenario, RNA-based NGS approach has emerged as an extremely useful tool for detecting these alterations. In this study, we report our NGS molecular records on ALK, ROS1, NTRK, and RET gene fusions and MET exon 14 skipping alterations detected by using a narrow RNA-based NGS panel, namely SiRe fusion.

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Introduction: Anaplastic lymphoma kinase (ALK) gene-rearrangements are identified in about 3-5% of non-small cell lung cancers (NSCLC), and ALK-rearranged NSCLC is to be considered an oncogene-addicted cancer with peculiar clinical characteristics.

Areas Covered: Several ALK inhibitors have been studied and approved for use in the treatment of advanced ALK-rearranged NSCLC with reported superiority in terms of efficacy and safety profile compared with chemotherapy. Second- and third-generation ALK inhibitors (alectinib, brigatinib, and lorlatinib) offer to NSCLC patients a clinically meaningful prolongment of survival with a very good quality of life profile.

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Patients with radically resected stage II and III NSCLC are exposed to a high risk of disease recurrence. Thus, adjuvant cisplatin-based chemotherapy is routinely offered to this patient population, although it results in an absolute increase in 5-year survival rate of only 4%. This modest improvement in survival rate makes it challenging to communicate to our patients about the decision to be treated with adjuvant chemotherapy or not.

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Background: MAURIS is an Italian multicenter, open-label, phase IIIb ongoing trial, aiming at evaluating the safety and effectiveness of atezolizumab + carboplatin/etoposide in patients with newly diagnosed, extensive-stage small-cell lung cancer (ES-SCLC). The primary objective is the safety evaluation.

Materials And Methods: Patients received atezolizumab + carboplatin/etoposide Q3W for 4-6 cycles in the induction phase, followed by atezolizumab maintenance Q3W.

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Article Synopsis
  • Platinum-based chemotherapy combined with immune-checkpoint inhibitors (ICIs) is a key treatment for advanced non-small cell lung cancer (NSCLC), but there's no randomized data to guide regimen selection.
  • A panel of experts reviewed available treatment data in July 2023 and agreed that the safety profile of chemo-ICI combinations is generally consistent and tolerable, though differences exist based on the specific ICI used.
  • The panel highlighted the importance of factors like PD-L1 levels and clinical characteristics in treatment choices, emphasizing the need for further research on anti-CTLA-4 impact, biomarker subgroups, and optimal treatment schedules.
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Background: The treatment of stage III non-small cell lung cancer (NSCLC) is very challenging because it is a heterogeneous group of diseases. This study was to investigative whether concurrent immunotherapy with chemoradiotherapy was associated with improved outcomes compared to consolidative immunotherapy following chemoradiotherapy in patients with unresectable stage III NSCLC, which may provide evidence-based medical evidence for the treatment of stage III NSCLC.

Methods: A total of 78 epidermal growth factor receptor or anaplastic lymphoma kinase (EGFR/ALK) negative patients from the clinical database of the shanghai pulmonary hospital with locally advanced unresectable NSCLC and we evaluated them for baseline clinical factors, follow-up.

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Background: ALK tyrosine kinase inhibitors (TKIs) have revolutionized the treatment and largely improved the survival outcomes of patients with NSCLC harboring rearrangements. Different ALK TKI compounds have demonstrated antitumor activity in these patients and are available in clinical practice. However, clinical expertise across countries varies according to local regulatory approval of different drugs, identifying multiple treatment scenarios to comply with international guidelines and clinical practice.

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Background: Pleural mesothelioma usually presents at an advanced, incurable stage. Chemotherapy with platinum-pemetrexed is a standard treatment. We hypothesised that the addition of pembrolizumab to platinum-pemetrexed would improve overall survival in patients with pleural mesothelioma.

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Taking into account the huge epidemiologic impact of lung cancer (in 2020, lung cancer accounted for 2,206,771 of the cases and for 1,796,144 of the cancer-related deaths, representing the second most common cancer in female patients, the most common cancer in male patients, and the second most common cancer in male and female patients) and the current lack of recommendations in terms of prognostic factors for patients selection and management, this article aims to provide an overview of the current landscape in terms of currently available immunotherapy treatments and the most promising assessed prognostic biomarkers, highlighting the current state-of-the-art and hinting at future challenges.

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Background: MET (MET Proto-Oncogene, Receptor Tyrosine Kinase) exon 14 skipping mutation represents one of the most common MET alterations, accounting for approximately 1-3% of all mutations in advanced lung adenocarcinomas. While until 2020 no specific treatment was available for this subset of patients, as of today, three MET Tyrosine Kinase Inhibitors (TKIs) are currently approved in this setting, namely capmatinib, tepotinib and savolitinib.

Objective: This article aims to provide an extensive overview of the current therapeutic standard of care for exon 14 skipped advanced Non-small Cell Lung Cancer (NSCLC) patients, alongside with mentions of the main future challenges and opportunities.

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Immune checkpoint inhibitors have changed the history of NSCLC treatment by becoming, alone or in combination with platinum-based chemotherapy, a mainstay of first-line therapy for advanced NSCLC. This increasingly dictates the identification of predictive biomarkers of response that can guide patient selection, in order to rationalize and personalize therapies, particularly in elderly patients. Immunotherapy in these patients raises questions of efficacy and tolerability related to aging, which is accompanied by a progressive decline in various body functions.

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Introduction: Lung cancer is the leading cause of cancer-related death worldwide, with non-small cell lung cancer (NSCLC) as the most common subtype. In the past decades, immunotherapy deeply changed paradigms for care of newly diagnosed advanced NSCLC patients without oncogenic driver mutations. An immunotherapy-based regimen alone or in combination to chemotherapy was crowned as the preferred option to choice, according to worldwide guideline.

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Objective: The primary goal of the Campania Oncology Network (ROC) was to reduce cancer delay and care fragmentation through the establishment of cancer-specific multidisciplinary oncologic groups (GOMs) and diagnostic and therapeutic assistance paths (PDTAs).

Methods: Five cancer centres of the ROC, with their own cancer specific GOM, were selected. In our analysis, we have focused on four neoplasms: lung, colon, ovarian and prostate cancers.

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Immune checkpoint inhibitors have activity in mesothelioma. IND.227 was a phase 2 trial (120 patients planned) comparing progression-free survival of standard platinum and pemetrexed (CP) versus CP + pembrolizumab (pembro) versus pembro.

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Article Synopsis
  • CTLA-4/PD-1/PD-L1 immune checkpoint inhibitors are standard treatments for advanced non-small cell lung cancer (NSCLC), but new monoclonal antibodies are emerging as potential therapies.
  • The paper aims to review both recently approved and emerging monoclonal antibody immune checkpoint inhibitors for NSCLC treatment.
  • More extensive studies and phase III trials are necessary to better understand the effectiveness of new ICIs and how they interact with the tumor microenvironment and patient selection.
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RET-selective tyrosine kinase inhibitors (TKIs) selpercatinib and pralsetinib have revolutionized the landscape of RET-positive (RET+) advanced non-small cell lung cancer (NSCLC) treatment, thanks to their efficacy and safety profiles. This class of medications currently represents the standard of care for both naïve and patients that have not received selective RET-TKIs in the first-line setting. However, we presently lack a satisfactory understanding of resistance mechanism developing after selective RET-TKIs usage, as well as a specific treatment for patients progressing on selpercatinib or pralsetinib.

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Background/aim: Lung cancer is one of the most common malignant neoplastic diseases and by far the leading cause of cancer death worldwide. Recently, immune checkpoint inhibitors (ICIs) have received increasing attention for playing a crucial role in non-small cell lung cancer (NSCLC). Biomarkers, such as programmed cell death-ligand 1 (PD-L1) and tumor mutational burden (TMB), seemed to be helpful in selecting patients who are more likely to benefit from ICI treatment: however, their role has not yet been fully clarified.

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Article Synopsis
  • Only two antiangiogenic monoclonal antibodies combined with EGFR-TKIs (erlotinib + bevacizumab and erlotinib + ramucirumab) are currently approved for treating EGFR+ advanced non-small cell lung cancer.
  • Patients eventually develop resistance to these treatments due to mechanisms like T790M substitutions and MET amplifications.
  • Osimertinib is the only approved option for T790M+ patients, but emerging data suggests MET-TKIs and combinations with chemotherapy/immunotherapy could improve treatment strategies in the future.
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Background: Nivolumab is the first programmed cell death receptor 1 (PD-1) inhibitor approved in China. Compared with chemotherapy, nivolumab has shown advantages of good efficacy and safety in the treatment of a variety of tumors. However, due to its short time of use in China and lack of safety experience, clinical understanding of its adverse reactions has not been sufficiently elucidated.

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Background: Brigatinib is a next-generation anaplastic lymphoma kinase (ALK) inhibitor with demonstrated efficacy in locally advanced and metastatic non-small cell lung cancer (NSCLC) in crizotinib-refractory and ALK inhibitor-naive settings. This analysis assessed brigatinib in Asian vs. non-Asian patients from the first-line ALTA-1L trial.

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Article Synopsis
  • Immune-checkpoint inhibitors (ICIs) are improving treatment options for patients with advanced stage non-small cell lung cancer (NSCLC), but their effectiveness in oncogene-addicted cases is still under debate.
  • The study analyzed 167 PD-L1 positive NSCLC patients to explore the presence of genomic alterations in five driver oncogenes.
  • Findings revealed that over half of the patients had genomic alterations, and despite these alterations, 37.5% of patients with high PD-L1 expression showed clinical benefit from ICIs.
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Article Synopsis
  • The genetic nature of cancer highlights the importance of molecular diagnoses and personalized treatments, especially for non-small cell lung cancer (NSCLC) patients with prevalent KRAS mutations, particularly KRAS G12C.
  • Sotorasib is noted as the first approved drug specifically targeting KRAS G12C mutations, providing significant clinical benefits for previously treated NSCLC patients.
  • Ongoing research focuses on overcoming resistance to KRAS inhibitors and exploring their effectiveness in combination with other therapies to enhance treatment outcomes for NSCLC patients with KRAS mutations.
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