Fusion detection and longitudinal circulating tumor DNA (ctDNA) profiling in ALK+ non-small cell lung cancer (NSCLC) patients.

Swalduz, Aurélie; Ortiz-Cuarán, Sandra; Avrillon, Virginie; Marteau, Solène; Martinez, Séverine; Clapisson, Gilles; Montané, Laure; Pérol, David; Green, Emma; Howarth, Karen; Kievit, Frank de; Morris, Clive; Pérol, Maurice; Saintigny, Pierre

doi:10.1200/jco.2018.36.15_suppl.e21031

Cited by 3 publications

(5 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Independently, these KDMs have been shown to be sensitive individually to lorlatinib in vitro and in vivo; however, to our knowledge this is the first time these two particular ALK mutations have been reported together conferring resistance to lorlatinib [19,30]. A recent case report detailed the presence of eight ALK KDMs in blood at progression on lorlatinib including F1174L and G1202R, further highlighting the complex resistance potential with multiple KDMs impeding drug binding ability and affinity [22]. Case 2 documents the emergence of the solvent front G1202R ALKi resistance mutation in variant 1.…”

Section: Discussionmentioning

confidence: 92%

“…In the first instance of CNS progression, her dose of brigatinib was uptitrated to enable higher drug exposure in the brain. Challenges were encountered in obtaining genetic information at progression, with plasma negative for ctDNA [22], as Mrs. ND underwent a craniotomy to resect monoprogressive symptomatic disease. Genetic analysis identified EML4-ALK variant 3 and an ALK G1202R panresistant KDM.…”

Section: Discussionmentioning

confidence: 99%

“…A plasma sample was next obtained to evaluate circulating tumor (ct) DNA via next-generation sequencing (NGS) (ctDx; Resolution Bioscience); however, this was uninformative, isolating no detectable genetic alteration (supplemental online Appendix 1A) [22]. There was no safe solid organ site to biopsy.…”

Section: Repeat Brain Imaging Was Stablementioning

confidence: 99%

See 2 more Smart Citations

ALK-Rearranged Non-Small Cell Lung Cancer in 2020: Real-World Triumphs in an Era of Multigeneration ALK-Inhibitor Sequencing Informed by Drug Resistance Profiling

et al. 2020

View full text Add to dashboard Cite

Since its discovery in 2007, we have seen the lives of patients diagnosed with advanced anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancers (NSCLC) transform with the advent of molecular therapies with first-, second-, and third-generation ALK inhibitors now available in the clinic. Despite great gains in patient survival now measured in years and preserved quality of life with targeted therapies, drug resistance is unfortunately inevitably encountered in this rare and unique molecular subset of lung cancer, and patients will eventually succumb to the disease. As these patients are often young, fit, and never smokers, the clinical and scientific communities have aligned to expedite drug development and access. Drug resistance profiling and further strategies are being explored through clinical trials, including the evaluation of specific drug sequencing and combinations to overcome such resistance and promote patient longevity. The cases of this report focus on precision medicine and aim to portray the pertinent aspects to consider when treating ALK-rearranged NSCLC in 2020, an ever-shifting space. By way of case examples, this report offers valuable information to the treating clinician, including the evolution of systemic treatments and the management of oligo-progression and multisite drug resistance. With the maturation of real-world data, we are fortunate to be experiencing quality and length of life for patients with this disease surpassing prior expectations in advanced lung cancer. The Oncologist 2020;25:641-649 KEY POINTS • This report focuses on the importance of genetic analysis of serial biopsies to capture the dynamic therapeutic vulnerabilities of a patient's tumor, providing a perspective on the complexity of ALK tyrosine kinase inhibitor (ALKi) treatment sequencing. • These case examples contribute to the literature on ALK-rearranged and oncogene addicted non-small cell lung cancer (NSCLC), providing a framework for care in the clinic. • In oligo-progressive disease, local ablative therapy and continuation of ALKi postprogression should be considered with potential for sustained disease control.

show abstract

Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

ALK-Rearranged Non-Small Cell Lung Cancer in 2020: Real-World Triumphs in an Era of Multigeneration ALK-Inhibitor Sequencing Informed by Drug Resistance Profiling

et al. 2020

View full text Add to dashboard Cite

show abstract

“…The clinical utility of ctDNA regarding recurrence in ALK-rearranged NSCLC has been shown in numerous studies [86][87][88][89][90][91][92][93][94]. In patients with ALK-positive NSCLC, ctDNA levels have been associated with disease burden being useful as surrogate marker of MRD.…”

Section: Alk Rearrangements As a Surrogate Mrd Markermentioning

confidence: 99%

Prognostic Value of Circulating Tumor DNA (ctDNA) in Oncogene-Driven NSCLC: Current Knowledge and Future Perspectives

Zografos

Dimitrakopoulos

Koutras

2022

Cancers

View full text Add to dashboard Cite

As we enter an unprecedented era of personalized medicine, molecular targeted therapies have the potential to induce improved survival outcome in patients with non-small cell lung cancer (NSCLC). However, a significant percentage of oncogene-driven NSCLC patients will relapse even after definitive treatment, whereas chronic and durable response to targeted therapies is a less common event in advanced-stage lung cancer. This phenomenon could be attributed to minimal residual disease (MRD), defined as a population of disseminated tumor cells that survive during the course or after treatment, eventually leading to recurrence and limiting patient survival. Circulating tumor DNA (ctDNA) is a powerful biomarker for MRD detection and monitoring and is a non-invasive approach of treating cancer, and especially NSCLC, based on a real-time assessment of the tumor genomic landscape. In this review, we present the key findings of studies that have used ctDNA with regard to its prognostic value and in respect to the most common druggable driver mutations of genes in NSCLC, such as epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), c-ros oncogene 1 (ROS1), rearranged during transfection (RET), Kirsten rat sarcoma virus (KRAS), B-Raf proto-oncogene (BRAF), and mesenchymal epithelial transition factor receptor (MET).

show abstract

“…At the time of progression, ALK mutations were identified in ctDNA that potentially caused treatment failure [118]. Thus, ctDNA can be used to monitor NSCLC treatment response as a surrogate MRD marker, since tumors responding to the treatment shed less DNA in the blood [132,133]. Prospective pre-TKI plasma collection allows comparison of relapse and baseline samples, for precise therapeutic monitoring and tracking of resistance [104].…”

Section: Alk-focused Diagnostic Studiesmentioning

confidence: 99%

New Advances in Liquid Biopsy Technologies for Anaplastic Lymphoma Kinase (ALK)—Positive Cancer

Villa

Sharma

Manfroni

et al. 2021

Cancers

View full text Add to dashboard Cite

Cancer cells are characterized by high genetic instability, that favors tumor relapse. The identification of the genetic causes of relapse can direct next-line therapeutic choices. As tumor tissue rebiopsy at disease progression is not always feasible, noninvasive alternative methods are being explored. Liquid biopsy is emerging as a non-invasive, easy and repeatable tool to identify specific molecular alterations and monitor disease response during treatment. The dynamic follow-up provided by this analysis can provide useful predictive information and allow prompt therapeutic actions, tailored to the genetic profile of the recurring disease, several months before radiographic relapse. Oncogenic fusion genes are particularly suited for this type of analysis. Anaplastic Lymphoma Kinase (ALK) is the dominant driver oncogene in several tumors, including Anaplastic Large-Cell Lymphoma (ALCL), Non-Small Cell Lung Cancer (NSCLC) and others. Here we review recent findings in liquid biopsy technologies, including ctDNA, CTCs, exosomes, and other markers that can be investigated from plasma samples, in ALK-positive cancers.

show abstract

Fusion detection and longitudinal circulating tumor DNA (ctDNA) profiling in ALK+ non-small cell lung cancer (NSCLC) patients.

Cited by 3 publications

References 0 publications

ALK-Rearranged Non-Small Cell Lung Cancer in 2020: Real-World Triumphs in an Era of Multigeneration ALK-Inhibitor Sequencing Informed by Drug Resistance Profiling

ALK-Rearranged Non-Small Cell Lung Cancer in 2020: Real-World Triumphs in an Era of Multigeneration ALK-Inhibitor Sequencing Informed by Drug Resistance Profiling

Prognostic Value of Circulating Tumor DNA (ctDNA) in Oncogene-Driven NSCLC: Current Knowledge and Future Perspectives

New Advances in Liquid Biopsy Technologies for Anaplastic Lymphoma Kinase (ALK)—Positive Cancer

Contact Info

Product

Resources

About