https://iris.unito.it/bitstream/2318/1677658/1/OP-ANNO180277%20192..237.pdf

Metastatic non-small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up †

Importance Non–small cell lung cancer remains the leading cause of cancer death in the United States. Until the last decade, the 5-year overall survival rate for patients with metastatic non–small cell lung cancer was less than 5%. Improved understanding of the biology of lung cancer has resulted in the development of new biomarker–targeted therapies and led to improvements in overall survival for patients with advanced or metastatic disease. Observations Systemic therapy for metastatic non–small cell lung cancer is selected according to the presence of specific biomarkers. Therefore, all patients with metastatic non–small cell lung cancer should undergo molecular testing for relevant mutations and expression of the protein PD-L1 (programmed death ligand 1). Molecular alterations that predict response to treatment (eg,EGFRmutations,ALKrearrangements,ROS1rearrangements, andBRAFV600E mutations) are present in approximately 30% of patients with non–small cell lung cancer. Targeted therapy for these alterations improves progression-free survival compared with cytotoxic chemotherapy. For example, somatic activating mutations in theEGFRgene are present in approximately 20% of patients with advanced non–small cell lung cancer. Tyrosine kinase inhibitors such as gefitinib, erlotinib, and afatinib improve progression-free survival in patients with susceptibleEGFRmutations. In patients with overexpression of ALK protein, the response rate was significantly better with crizotinib (a tyrosine kinase inhibitor) than with the combination of pemetrexed and either cisplatin or carboplatin (platinum-based chemotherapy) (74% vs 45%, respectively;P  Conclusions and Relevance Improved understanding of the biology and molecular subtypes of non–small cell lung cancer have led to more biomarker-directed therapies for patients with metastatic disease. These biomarker-directed therapies and newer empirical treatment regimens have improved overall survival for patients with metastatic non–small cell lung cancer.

https://jamanetwork.com/journals/jama/articlepdf/2748800/jama_arbour_2019_rv_190008.pdf

Systemic Therapy for Locally Advanced and Metastatic Non-Small Cell Lung Cancer: A Review.

https://repub.eur.nl/pub/129868/Repub_129868.pdf

Recommendations for the use of next-generation sequencing (NGS) for patients with metastatic cancers: a report from the ESMO Precision Medicine Working Group.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer (NSCLC) address all aspects of management for NSCLC. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines regarding targeted therapies, immunotherapies, and their respective biomarkers.

/pdf/nccn-guidelines-insights-non-small-cell-lung-cancer-version-1ba22557nk.pdf

NCCN Guidelines Insights: Non–Small Cell Lung Cancer, Version 2.2021

The impressive clinical activity of small-molecule receptor tyrosine kinase inhibitors for oncogene-addicted subgroups of non-small-cell lung cancer (for example, those driven by activating mutations in the gene encoding epidermal growth factor receptor (EGFR) or rearrangements in the genes encoding the receptor tyrosine kinases anaplastic lymphoma kinase (ALK), ROS proto-oncogene 1 (ROS1) and rearranged during transfection (RET)) has established an oncogene-centric molecular classification paradigm in this disease. However, recent studies have revealed considerable phenotypic diversity downstream of tumour-initiating oncogenes. Co-occurring genomic alterations, particularly in tumour suppressor genes such as TP53 and LKB1 (also known as STK11), have emerged as core determinants of the molecular and clinical heterogeneity of oncogene-driven lung cancer subgroups through their effects on both tumour cell-intrinsic and non-cell-autonomous cancer hallmarks. In this Review, we discuss the impact of co-mutations on the pathogenesis, biology, microenvironmental interactions and therapeutic vulnerabilities of non-small-cell lung cancer and assess the challenges and opportunities that co-mutations present for personalized anticancer therapy, as well as the expanding field of precision immunotherapy.

/pdf/co-occurring-genomic-alterations-in-non-small-cell-lung-3ouk4bpagi.pdf

Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy

Background Brigatinib, a next-generation anaplastic lymphoma kinase (ALK) inhibitor, has robust efficacy in patients with ALK-positive non–small-cell lung cancer (NSCLC) that is refractory to crizotinib. The efficacy of brigatinib, as compared with crizotinib, in patients with advanced ALK-positive NSCLC who have not previously received an ALK inhibitor is unclear. Methods In an open-label, phase 3 trial, we randomly assigned, in a 1:1 ratio, patients with advanced ALK-positive NSCLC who had not previously received ALK inhibitors to receive brigatinib at a dose of 180 mg once daily (with a 7-day lead-in period at 90 mg) or crizotinib at a dose of 250 mg twice daily. The primary end point was progression-free survival as assessed by blinded independent central review. Secondary end points included the objective response rate and intracranial response. The first interim analysis was planned when approximately 50% of 198 expected events of disease progression or death had occurred. Results A total o...

https://www.nejm.org/doi/pdf/10.1056/NEJMoa1810171

Brigatinib versus Crizotinib in ALK-Positive Non-Small-Cell Lung Cancer

Background A splice-site mutation that results in a loss of transcription of exon 14 in the oncogenic driver MET occurs in 3 to 4% of patients with non–small-cell lung cancer (NSCLC). We e...

https://www.nejm.org/doi/pdf/10.1056/NEJMoa2004407

Gee Chen Chang

Papers

Brigatinib versus Crizotinib in ALK-Positive Non-Small-Cell Lung Cancer

Tepotinib in Non–Small-Cell Lung Cancer with MET Exon 14 Skipping Mutations