Dataset Information

Sustained Improvement in the Management of Patients with Non-Small-Cell Lung Cancer (NSCLC) Harboring ALK Translocation: Where Are We Running?

ABSTRACT: ALK translocation amounts to around 3-7% of all NSCLCs. The clinical features of ALK+ NSCLC are an adenocarcinoma histology, younger age, limited smoking history, and brain metastases. The activity of chemotherapy and immunotherapy is modest in ALK+ disease. Several randomized trials have proven that ALK inhibitors (ALK-Is) have greater efficacy with respect to platinum-based chemotherapy and that second/third generation ALK-Is are better than crizotinib in terms of improvements in median progression-free survival and brain metastases management. Unfortunately, most patients develop acquired resistance to ALK-Is that is mediated by on- and off-target mechanisms. Translational and clinical research are continuing to develop new drugs and/or combinations in order to raise the bar and further improve the results attained up to now. This review summarizes first-line randomized clinical trials of several ALK-Is and the management of brain metastases with a focus on ALK-I resistance mechanisms. The last section addresses future developments and challenges.

SUBMITTER: Spitaleri G

PROVIDER: S-EPMC10217667 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

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Publications

Sustained Improvement in the Management of Patients with Non-Small-Cell Lung Cancer (NSCLC) Harboring ALK Translocation: Where Are We Running?

Spitaleri Gianluca G Trillo Aliaga Pamela P Attili Ilaria I Del Signore Ester E Corvaja Carla C Corti Chiara C Crimini Edoardo E Passaro Antonio A de Marinis Filippo F

Current oncology (Toronto, Ont.) 20230516 5

ALK translocation amounts to around 3-7% of all NSCLCs. The clinical features of ALK+ NSCLC are an adenocarcinoma histology, younger age, limited smoking history, and brain metastases. The activity of chemotherapy and immunotherapy is modest in ALK+ disease. Several randomized trials have proven that ALK inhibitors (ALK-Is) have greater efficacy with respect to platinum-based chemotherapy and that second/third generation ALK-Is are better than crizotinib in terms of improvements in median progre ...[more]

PMID: 37232842

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Project description:ImportanceDeregulation of anaplastic lymphoma kinase (ALK) occurs in 3-7% of advanced NSCLC mainly because of chromosomic rearrangements at the ALK locus. Next to its oncogenic function, ALK chimeric oncoprotein is a possible antigen for human immune system. The prognostic value of natural anti-ALK immunogenicity remains poorly explored in ALK + NSCLC. We hereby report preliminary results of a plasmatic anti-ALK a-abs titration assessment in a cohort of ALK + NSCLC pts.ObjectiveTo evaluate the prevalence of pre-existing circulating anti-ALK a-abs in ALK + NSCLC pts. Key secondary objectives are the assessment of anti-ALK a-abs prognostic value and association with brain metastases (BM).DesignThis monocentric case series included 60 ALK + NSCLC pts progressing on any anti-ALK TKIs between October 2015 and February 2021 at Gustave Roussy Cancer Campus. Fifty-six plasma samples were analyzed through a semiquantitative immunocytochemical technique. Plasma samples were obtained from two prospective studies approved by our Institutional Review Board: the MATCH-R trial (NCT02517892) and the MSN trial (RECF1256).ParticipantsWe included pts diagnosed with unresectable stage III or IV NSCLC, either by contemporaneous or historical biopsy. ALK-rearrangement was identified by FISH, IHC or NGS. Pts were aged more than 18-year-old and had previously signed informed consent for one of the studies. Pts had received at least one anti-ALK-TKI during the disease history. Pts were not eligible if they had been diagnosed with a second cancer.Main outcomes and measuresThe prevalence of plasmatic anti-ALK a-abs titer was reported as percentage. Progression-free survival, overall survival, and time to BM were analyzed using Kaplan-Meier methods.ResultsWe found an anti-ALK a-abs titer in 5 (9 %) pts. anti-ALK a-abs did not contribute to prolongation of survival. Although not significant, there was a trend towards protection against BM in the presence of anti-ALK a-abs.Conclusions and relevanceBecause ALK fusion proteins are exclusively produced intracellularly, not all ALK autoantibodies may have direct anti-tumor impact with favorable prognostic value. This is the first investigation to explore the impact of circulating anti-ALK a-abs on BM. Prospective studies with longer follow-up are warranted to further explore the impact of anti-ALK a-abs on BM.

Dataset Information

Sustained Improvement in the Management of Patients with Non-Small-Cell Lung Cancer (NSCLC) Harboring ALK Translocation: Where Are We Running?

Publications

Sustained Improvement in the Management of Patients with Non-Small-Cell Lung Cancer (NSCLC) Harboring ALK Translocation: Where Are We Running?

Similar Datasets

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