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

Purpose Approximately 1% to 2% of non-small-cell lung cancers (NSCLCs) harbor a c-ros oncogene 1 ( ROS1) rearrangement. Crizotinib, an inhibitor of anaplastic lymphoma kinase (ALK), ROS1, and MET, has shown marked antitumor activity in a small expansion cohort of patients with ROS1-positive advanced NSCLC from an ongoing phase I study. We assessed the efficacy and safety of crizotinib in the largest cohort of patients with ROS1-positive advanced NSCLC. Patients and Methods This phase II, open-label, single-arm trial enrolled East Asian patients with ROS1-positive (assessed through validated AmoyDx assay [Amoy Diagnostics, Xiamen, China] at three regional laboratories) advanced NSCLC who had received three or fewer lines of prior systemic therapies. Patients were to receive oral crizotinib at a starting dose of 250 mg twice daily and continued treatment until Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1-defined progression (by independent radiology review [IRR]), unacceptable toxicity, or withdrawal of consent. The primary end point was objective response rate (ORR) by IRR. Results In the efficacy and safety analyses, 127 patients were included, with 49.6% still receiving treatment at data cutoff. ORR by IRR was 71.7% (95% CI, 63.0% to 79.3%), with 17 complete responses and 74 partial responses. ORRs were similar irrespective of the number of prior lines of therapy, and responses were durable (median duration of response, 19.7 months; 95% CI, 14.1 months to not reached). Median progression-free survival by IRR was 15.9 months (95% CI, 12.9 to 24.0 months). No new safety signals associated with crizotinib were reported. Conclusion This study demonstrated clinically meaningful benefit and durable responses with crizotinib in East Asian patients with ROS1-positive advanced NSCLC. Crizotinib was generally well tolerated, with a safety profile consistent with previous reports.

https://ascopubs.org/doi/pdfdirect/10.1200/JCO.2017.75.5587

Phase II Study of Crizotinib in East Asian Patients With ROS1-Positive Advanced Non–Small-Cell Lung Cancer

The results of checking the domestic evacuation facility-related systems and problems from the design stage are summarized as follows. (1) One of the problems that is constantly pointed out in the current system is the lack of administrative consistency. For firefighting facilities installed in buildings, it is necessary to improve the system for the systematic application of the dual standards of building-related laws and fire-fighting-related laws. (2) Various measures are institutionally regulated for evacuation facilities in apartments that want to secure evacuation passages in two of more directions; however, there is insufficient review of the design plan that applies a modified form according to the architectural plan, so it is a step-by-step application system that is necessary to provide. (3) Products that can replace the existing evacuation facilities can be applied depending on the design situation of the apartment and have been released with the certification on the Ministry of Land, Infrastructure and Transport, but their utilization is insufficient. It is judged that it will not only improve the performance, but also solve the problems of the existing evacuation space and top-down evacuation area to some extent. (4) Although various evacuation facilities are being installed in newly built apartments through the process of changing the system, evacuation facilities are also applied to existing aged buildings through fire safety performance enhancement projects and green remodeling projects to ensure fire safety that is considered to be increased. Form the above results, it is necessary to systematically reorganize the scattered laws and regulations as there is a risk of fatal damage such as an apartment fire. It will be necessary to introduce an evacuation facility that can be used by all members, including children, the elderly, and the disabled, to secure fire safety performance. 

Dong Wan Kim

Papers

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

Phase II Study of Crizotinib in East Asian Patients With ROS1-Positive Advanced Non–Small-Cell Lung Cancer

Apartment Evacuation Facility-related Systems and Actual Conditions