Clinical Relevance of an Amplicon-Based Liquid Biopsy for Detecting<i>ALK</i>and<i>ROS1</i>Fusion and Resistance Mutations in Patients With Non–Small-Cell Lung Cancer

Mezquita, Laura; Swalduz, Aurélie; Jovelet, Cécile; Ortiz-Cuarán, Sandra; Howarth, Karen; Planchard, David; Avrillon, Virginie; Recondo, Gonzálo; Marteau, Solène; Benítez, José Carlos; Kievit, Frank de; Plagnol, Vincent; Lacroix, Ludovic; Odier, L.; Rouleau, Etienne; Fournel, P.; Caramella, Caroline; Tissot, Claire; Adam, Julien; Woodhouse, Samuel; Nicotra, Claudio; Auclin, Édouard; Remón, Jordi; Morris, Clive; Green, Emma; Massard, Christophe; Pérol, Maurice; Friboulet, Luc; Besse, Benjamin; Saintigny, Pierre

doi:10.1200/po.19.00281

Cited by 44 publications

(37 citation statements)

References 37 publications

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“…In February 2018, a 62-year-old woman with a previous light smoking history (five packs/year) was diagnosed with lung adenocarcinoma with pleural, pericardial, lymph nodal and bone metastases. After two cycles of first-line chemotherapy with cisplatin and pemetrexed (best response stable disease) and the detection of an EZR-ROS1 fusion on liquid biopsy (InVisionFirst-Lung amplicon-based assay), 6 confirmed by FISH on tumor sample, the patient received entrectinib 600 mg daily since July 2018. No relevant side effects were recorded and partial response was achieved after two months.…”

Section: Case Presentationmentioning

confidence: 99%

Meningeal “Lazarus Response” to Lorlatinib in a ROS1-Positive NSCLC Patient Progressing to Entrectinib

Facchinetti¹,

Lévy²,

Naltet³

et al. 2021

CMAR

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Background ROS1 tyrosine kinase inhibitors (TKIs) have showed activity and efficacy in ROS1 -rearranged non-small cell lung cancer (NSCLC). In the clinical practice, besides the utilization of crizotinib, less is known about the best treatment strategies involving additional, new-generation TKIs for the sequential treatment of ROS1-positive NSCLC patients. Case Presentation A patient suffering from a ROS1 -rearranged lung adenocarcinoma, after receiving cisplatin-pemetrexed chemotherapy, was treated with entrectinib, a new-generation ALK/ROS1/NTRK inhibitor. After 16 months, central nervous system (CNS) metastases appeared, without extra-cerebral disease progression. Stereotactic brain radiotherapy was performed and entrectinib was maintained, due to the global systemic disease control. Approximately one month after radiotherapy, thoracic and meningeal progressions were detected, the latter highly symptomatic with neurocognitive disorders, visual hallucinations and worsening of psycho-motor impairment. A lumbar puncture was positive for tumor cells and for an EZR-ROS1 fusion. The administration of lorlatinib (a third-generation ALK/ROS1 inhibitor) prompted an extremely rapid improvement of clinical conditions, anticipating the positive results observed at radiologic evaluation that confirmed the disease response still ongoing after nine months since treatment start. Discussion With the expanding availability of targeted agents with differential activity on resistance mechanism and on CNS disease, choosing wisely the best treatment strategies is pivotal to assure the best clinical outcomes in oncogene-addicted NSCLC patients. Here we have reported lorlatinib reverted an almost fatal meningeal carcinomatosis developing during entrectinib in a ROS1-positive NSCLC patient.

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Section: Case Presentationmentioning

confidence: 99%

Meningeal “Lazarus Response” to Lorlatinib in a ROS1-Positive NSCLC Patient Progressing to Entrectinib

Facchinetti¹,

Lévy²,

Naltet³

et al. 2021

CMAR

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“…The ROS1 p. G2032R resistance mutation was found in 30% of evaluated cases. Patients with no detectable mutations in ctDNA had a longer median overall survival despite progression on TKIs [ 63 ].…”

Section: Available Assays and Target Genomic Alterations In Lung Cmentioning

confidence: 99%

The Role of the Liquid Biopsy in Decision-Making for Patients with Non-Small Cell Lung Cancer

Akhoundova

Martinez²,

Musmann

et al. 2020

JCM

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Liquid biopsy is a rapidly emerging tool of precision oncology enabling minimally invasive molecular diagnostics and longitudinal monitoring of treatment response. For the clinical management of advanced stage lung cancer patients, detection and quantification of circulating tumor DNA (ctDNA) is now widely adopted into clinical practice. Still, interpretation of results and validation of ctDNA-based treatment decisions remain challenging. We report here our experience implementing liquid biopsies into the clinical management of lung cancer. We discuss advantages and limitations of distinct ctDNA assay techniques and highlight our approach to the analysis of recurrent molecular alterations found in lung cancer. Moreover, we report three exemplary clinical cases illustrating the complexity of interpreting liquid biopsy results in clinical practice. These cases underscore the potential and current limitations of liquid biopsy, focusing on the difficulty of interpreting discordant findings. In our view, despite all current limitations, the analysis of ctDNA in lung cancer patients is an essential and highly versatile complementary diagnostic tool for the clinical management of lung cancer patients in the era of precision oncology.

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“…While the detection from tissue samples is routinely implemented as a gold standard, liquid biopsies are not well established and are challenging in this setting (8). Importantly, recent reports et al reported a sensitivity of 67% at baseline, 46% at progression, and 11% under treatment, respectively for ALK and ROS1 rearrangements using the InVisionFirst-Lung NGS assay (Inivata, Morrisville, NC-USA) for plasma testing and a combination of FISH, IHC, and NGS for tissue testing (13). Interestingly and in line with the results reported in this study, a higher detection rate was observed in patients at progression than those under active anti-ALK treatment, suggesting that longitudinal tracking of ALK rearrangements under treatment might be predictive of response to therapy.…”

Section: Discussionmentioning

confidence: 99%

Detection of ALK fusion transcripts in plasma of non-small cell lung cancer patients using a novel RT-PCR based assay

et al. 2021

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Background: Detection of genomic rearrangements, like anaplastic lymphoma kinase (ALK) fusions, is a pivotal requirement in non-small cell lung cancer (NSCLC) for the initiation of a targeted treatment. While tissue testing remains the gold standard, detection of these alterations using liquid biopsies is an unmet need.To enable the detection of ALK rearrangements from circulating-free RNA (cfRNA) from NSCLC patients, we have evaluated a novel reverse transcription PCR (RT-PCR) based assay.Methods: Sixty-six patients with advanced stage NSCLC were included in the study. ALK status was determined by immunohistochemistry (IHC) and/or FISH on tissue sections. For the detection of ALK rearrangements from 2ml plasma collected in EDTA or Streck BCT DNA tubes, cfRNA was extracted using a prototype cfRNA sample preparation method and tested by a novel multiplex ALK/RET RT-PCR assay (Roche).Results: Of the forty-two patients with an ALK rearrangement, 30 (71%) were included at baseline. In 10 of the baseline patients, an ALK rearrangement was detected by RT-PCR [baseline sensitivity 33.33% (95% CI: 17.29-52.81%)]. All 24 negative ALK IHC/FISH-negative patients were negative using the RT-PCR based assay (specificity =100%). Conclusions:The prototype Roche ALK/RET RT-PCR assay was able to detect ALK fusion transcripts in the plasma of NSCLC patients at baseline as well as at disease progression with limited sensitivity but high

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Clinical Relevance of an Amplicon-Based Liquid Biopsy for DetectingALKandROS1Fusion and Resistance Mutations in Patients With Non–Small-Cell Lung Cancer

Cited by 44 publications

References 37 publications

Meningeal “Lazarus Response” to Lorlatinib in a ROS1-Positive NSCLC Patient Progressing to Entrectinib

Meningeal “Lazarus Response” to Lorlatinib in a ROS1-Positive NSCLC Patient Progressing to Entrectinib

The Role of the Liquid Biopsy in Decision-Making for Patients with Non-Small Cell Lung Cancer

Detection of ALK fusion transcripts in plasma of non-small cell lung cancer patients using a novel RT-PCR based assay

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