Expanding anaplastic lymphoma kinase therapeutic indication to early stage non-small cell lung cancer

Abstract

Oncogene-addicted non-small cell lung cancer (NSCLC) patients have been witnessing overwhelming therapeutic improvements, especially in advanced disease management, due to the advent of more potent tyrosine kinase inhibitors (TKIs). However, the concrete chance to cure anaplastic lymphoma kinase (ALK)-rearranged patients remains prerogative of surgical and peri-operative medical approaches to early disease stage. Clinical investigations in the adjuvant setting of genotype-restricted lung cancers (i.e., EGFR+, ALK+, etc.) are under-represented owing to the need of large patients' enrollment and solid overall survival (OS) data, which solely can show real long-term impact of these therapeutic interventions. Current available radiological and molecular technologies will widely increase the number of surgical early stage patients, including ALK+, spurring the development of rational approaches aimed to prevent disease recurrence and prolong patients' survival. Ongoing clinical trials, evaluating crizotinib and alectinib as adjuvant treatments, will gauge the real impact of TKIs in terms of patients' disease free survival (DFS) and OS; other peri-operative investigations (e.g., neo-adjuvant strategies) will add information about ALK inhibitors' tumor growth restraint capacities and early adaptation mechanisms to ALK targeting. Nevertheless, multiple questions are and will remain unanswered: if should be treated indifferently all ALK+ patients or, alternatively, should be stratified in different risk groups based on the detectable residual disease [i.e., minimal residual disease (MRD) after surgery]; whether ALK inhibitors administration could facilitate the accumulations of persister cells driving resistance mechanisms to targeted therapies; if alternative strategies, as combined treatments targeting different molecular hubs, could enhance disease control and cancer eradication.

Analysis of Molecular Biomarkers in Resected Early-Stage Non-Small Cells Lung Cancer: A Narrative Review

“…Accordingly, more clinical trials are needed with the aim of better understanding earlystage ALK-positive NSCLC. A comprehensive molecular analysis of the entire population of resected lung tumours is necessary-new generation platforms based on the multigene analyses of DNA and RNA should be exploited to highlight the presence of ALK fusions in early-stage tumours [27].…”

Prospects for the development of adjuvant therapy for non-small cell lung cancer

“…После адъювантного лечения будет осуществляться разделение на 2 рукава: получение кризотиниба в стандартной дозе в течение 24 мес или наблюдение. Первичная конечная точка -БРВ, вторичные -ОВ, токсичность, безопасность [14].…”

Early-stage ALK-positive lung cancer: a narrative review

“…The objective of this narrative review is to summarize the literature regarding the prevalence and prognosis of early-stage ALK -positive NSCLC and the utility of targeted therapy, immunotherapy, and chemotherapy in the neoadjuvant and adjuvant settings. While previous reviews have summarized the frequency of early-stage ALK -positive NSCLC and challenges in conducting adjuvant ALK inhibitor clinical trials, they were completed several years ago, during which additional clinical trials have opened and closed ( 14 - 16 ). We present this article in accordance with the Narrative Review reporting checklist (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-22-631/rc ).…”