In recent years, advanced non-small-cell lung cancer has undergone tremendous progress in its management. On the one hand, the use of immune checkpoints inhibitors (anti-PD-(L)1 and anti-CTLA4) with or without chemotherapy has revolutionized the prognosis of a relevant number of patients; on the other hand, the discovery of several actionable genetic drivers in adenocarcinoma histology, configuring oncogene addicted disease, has paved the way for the implementation in clinical practice of precision medicine. More in detail, numerous targeted drugs are now available against specific molecular alterations, all having shown robust anti-tumor activity at the cost of manageable toxicity.

Against this background, it is clear that the treatment of advanced non-small-cell lung cancer has become complex, currently requiring high standards of expertise as well as the availability of accurate molecular diagnostic techniques. In the present special issue, we aim to provide the reader with the latest developments in the diagnosis and therapeutic management of advanced non-small-cell lung cancer, assuming that we face not one but many disease entities with peculiar prognoses and responses to treatment.

Non-small-cell lung cancer: how to manage MET exon 14 skipping mutant disease

Juan Bautista Blaquier, Gonzalo Recondo

Article Type

Review

Published

In this article, the authors focus on the management of patients with MET exon 14 skipping alterations by addressing the biology of the MET receptor and exon 14 skipping mutations, current treatment strategies, and sequential treatment options based on resistance mechanisms to MET inhibitors in patients with non-small-cell lung cancer.

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Advanced non-small-cell lung cancer: how to manage non-oncogene disease

Andrea De Giglio, Alessandro Di Federico, Chiara Deiana, Biagio Ricciuti, Marta Brambilla, Giulio Metro

Article Type

Review

Published

This article provides a review of the current treatment approaches to advanced non-small-cell lung cancer in patients without molecular driver alterations, with an additional focus on special populations, concomitant medications, and other considerations that might be useful for daily clinical practice.

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Non-small-cell lung cancer: how to manage RET-positive disease

Elisa Andrini, Mirta Mosca, Linda Galvani, Francesca Sperandi, Biagio Ricciuti, Giulio Metro, Giuseppe Lamberti

Article Type

Review

Published

This article reviews the biology, clinicopathological characteristics, targeted therapies and mechanisms of resistance of advanced non-small-cell lung cancer harbouring RET fusions to provide treatment guidance for these patients.

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Advanced non-small-cell lung cancer: how to manage EGFR and HER2 exon 20 insertion mutation-positive disease

Giulio Metro, Andrea De Giglio, Biagio Ricciuti, Marco Siringo, Daniele Marinelli, Alain Gelibter, Federica Pecci, Rossana Berardi, Luca Cantini, Alessandro Di Federico, Elisa Andrini, Mirta Mosca, Giuseppe Lamberti, Marta Brambilla, Giannis Mountzios

Article Type

Review

Published

The authors provide a concise but comprehensive summary of the challenges that lie ahead as we move towards personalized treatment of Ex20ins-mutant and HER2-mutant advanced NSCLC, also suggesting a treatment algorithm that could be followed for patients with these genetic aberrations.

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Non-small-cell lung cancer: how to manage EGFR-mutated disease

Federica Pecci, Luca Cantini, Giulio Metro, Biagio Ricciuti, Giuseppe Lamberti, Ammad Ahmad Farooqi, Rossana Berardi

Article Type

Review

Published

The authors provide an updated and comprehensive summary of the latest advancements in the quest for compounds targeting EGFR-mutant advanced non-small-cell lung cancer, discussing the biological rationale underlying the development of a forefront combination of TKI and/or new antibody–drug conjugates.

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Non-small-cell lung cancer: how to manage ALK-, ROS1- and NTRK-rearranged disease

Daniele Marinelli, Marco Siringo, Giulio Metro, Biagio Ricciuti, Alain J Gelibter

Article Type

Review

Published

ALK-, ROS1- and NTRK-rearranged tumours represent a distinct clinical and molecular entity amongst non-small-cell lung cancer and have the highest frequency amongst young, non-smoker patients. This paper discusses ALK, ROS1 and NTRK-rearranged disease and all the available treatments are evaluated.

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How to manage KRAS G12C-mutated advanced non-small-cell lung cancer

Biagio Ricciuti, Alessia Mira, Elisa Andrini, Pietro Scaparone, Sandra Vietti Michelina, Federica Pecci, Luca Cantini, Andrea De Giglio, Giuseppe Lamberti, Chiara Ambrogio, Giulio Metro

Article Type

Review

Published

The authors review the current treatment landscape for patients with advanced non-small-cell lung cancers harbouring a KRAS G12C mutation, including PD-(L) 1-based therapies and direct KRAS inhibitors as well as sequential treatment options.

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