Current treatment and future challenges in ROS1- and ALK-rearranged advanced non-small cell lung cancer

Remón, Jordi; Pignataro, Daniele; Novello, Silvia; Passiglia, Francesco

doi:10.1016/j.ctrv.2021.102178

Cited by 50 publications

(36 citation statements)

References 97 publications

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“…ALK and ROS1 rearrangements have been proved as oncogenic drivers. Tejas Patil et al, reviewed 579 patients with stage IV NSCLC, and the results showed that the incidence of brain metastases for treatment-naïve, stage IV ROS1+ and ALK+ NSCLC were both up to about 34% and with no difference across ROS1, ALK, EGFR, KRAS, BRAF or other mutations groups [ 27 , 28 ].…”

Section: Discussionmentioning

confidence: 99%

Prognosis of lung cancer with simple brain metastasis patients and establishment of survival prediction models: a study based on real events

et al. 2022

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Objectives The aim of this study was to explore risk factors for the prognosis of lung cancer with simple brain metastasis (LCSBM) patients and to establish a prognostic predictive nomogram for LCSBM patients. Materials and methods Three thousand eight hundred and six cases of LCSBM were extracted from the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2015 using SEER Stat 8.3.5. Lung cancer patients only had brain metastasis with no other organ metastasis were defined as LCSBM patients. Prognostic factors of LCSBM were analyzed with log-rank method and Cox proportional hazards model. Independent risk and protective prognostic factors were used to construct nomogram with accelerated failure time model. C-index was used to evaluate the prediction effect of nomogram. Results and conclusion The younger patients (18–65 years old) accounted for 54.41%, while patients aged over 65 accounted for 45.59%.The ratio of male: female was 1:1. Lung cancer in the main bronchus, upper lobe, middle lobe and lower lobe were accounted for 4.91%, 62.80%, 4.47% and 27.82% respectively; and adenocarcinoma accounted for 57.83% of all lung cancer types. The overall median survival time was 12.2 months. Survival rates for 1-, 3- and 5-years were 28.2%, 8.7% and 4.7% respectively. We found female (HR = 0.81, 95% CI 0.75–0.87), the married (HR = 0.80; 95% CI 0.75–0.86), the White (HR = 0.90, 95% CI 0.84–0.95) and primary site (HR = 0.45, 95% CI 0.39–0.52) were independent protective factors while higher age (HR = 1.51, 95% CI 1.40–1.62), advanced grade (HR = 1.19, 95% CI 1.12–1.25) and advanced T stage (HR = 1.09, 95% CI 1.05–1.13) were independent risk prognostic factors affecting the survival of LCSBM patients. We constructed the nomogram with above independent factors, and the C-index value was 0.634 (95% CI 0.622–0.646). We developed a nomogram with seven significant LCSBM independent prognostic factors to provide prognosis prediction.

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Section: Discussionmentioning

confidence: 99%

Prognosis of lung cancer with simple brain metastasis patients and establishment of survival prediction models: a study based on real events

et al. 2022

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“…ALK rearrangements are detected in approximately 5% of non-squamous NSCLCs, while the occurrence of ROS1 and RET translocations is around 2%. These gene fusions have increased prevalence in young NSCLC patients and, similarly to EGFR and ALK, are typical for female and smoking-unrelated tumors [20][21][22][23]. NSCLCs carrying druggable rearranged kinases demonstrate spectacular benefit from targeted therapies: several studies involving metastatic NSCLC cases produced median overall survival estimates well above five years, with some categories of patients approaching close to ten years survival threshold [24][25][26].…”

Section: Non-small Cell Lung Cancer (Nsclc)mentioning

confidence: 99%

Cancer Therapy Guided by Mutation Tests: Current Status and Perspectives

Aleksakhina

Imyanitov

2021

IJMS

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The administration of many cancer drugs is tailored to genetic tests. Some genomic events, e.g., alterations of EGFR or BRAF oncogenes, result in the conformational change of the corresponding proteins and call for the use of mutation-specific compounds. Other genetic perturbations, e.g., HER2 amplifications, ALK translocations or MET exon 14 skipping mutations, cause overproduction of the entire protein or its kinase domain. There are multilocus assays that provide integrative characteristics of the tumor genome, such as the analysis of tumor mutation burden or deficiency of DNA repair. Treatment planning for non-small cell lung cancer requires testing for EGFR, ALK, ROS1, BRAF, MET, RET and KRAS gene alterations. Colorectal cancer patients need to undergo KRAS, NRAS, BRAF, HER2 and microsatellite instability analysis. The genomic examination of breast cancer includes testing for HER2 amplification and PIK3CA activation. Melanomas are currently subjected to BRAF and, in some instances, KIT genetic analysis. Predictive DNA assays have also been developed for thyroid cancers, cholangiocarcinomas and urinary bladder tumors. There is an increasing utilization of agnostic testing which involves the analysis of all potentially actionable genes across all tumor types. The invention of genomically tailored treatment has resulted in a spectacular improvement in disease outcomes for a significant portion of cancer patients.

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“…Multiple fusion partners have been reported for ROS1 rearrangement, the most common of which being CD74 , followed by SDC4 , EZR , and SLC34A2 ( 2 ). Due to structural similarity, several tyrosine kinase inhibitors (TKIs) targeting anaplastic lymphoma kinase (ALK) or neurotrophin receptor tyrosine kinase (NTRK), such as crizotinib and entrectinib, have shown remarkable clinical efficacy and are currently recommended as first- or second-line therapy for ROS1 -positive NSCLC ( 3 ). In a phase II clinical trial of 127 East Asian patients treated with crizotinib, median progression-free survival (PFS) was 10.2 and 18.8 months in patients with and without baseline central nervous system (CNS) metastasis, respectively ( 4 ).…”

Section: Introductionmentioning

confidence: 99%

Case Report: Short-Term Response to First-Line Crizotinib Monotherapy in a Metastatic Lung Adenocarcinoma Patient Harboring a Novel TPR-ROS1 Fusion

Wei

Yang

et al. 2022

Front. Oncol.

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ROS1-rearranged patients account for 1-2% of non-small cell lung cancer (NSCLC) cases. Approximately 10 fusion partners have been discovered, while clinical practice is actively generating knowledge of new ones and their therapeutic responses. Herein, we report a patient with stage IV NSCLC that harbored a novel TPR-ROS1 fusion, which demonstrated a rapid but short partial response to first line crizotinib and primary resistance to subsequent ceritinib. Computed tomography detected a pulmonary nodule in a 53-year-old woman who presented with persistent cough. Histopathologic and molecular examination of the tissue biopsy indicated a poorly differentiated adenocarcinoma staining negative for PD-L1 but harbored a novel translocated promoter region (TPR)-ROS1 (T4:R35) gene fusion. Frontline crizotinib monotherapy elicited a rapid partial response after 1 month, although the disease progressed another 2 months later. After another 3 months of continued crizotinib treatment, the patient manifested newly emerged and enlarged lung and brain lesions. Genomic profiling still identified TPR-ROS1 as the only aberration, while a lymph node biopsy indicated PD-L1 immunopositivity. The patient was then treated with ceritinib and progressed within 1 month. She was started on chemotherapy with pemetrexed plus carboplatin and has achieved rapid partial response as of the latest follow-up. In summary, we provided clinical evidence of a novel TPR-ROS1 fusion and its roles as an oncogenic driver in metastatic NSCLC. To the best of our knowledge, ours is the first case to report this fusion in NSCLC. This case was characterized by a rapid yet short-term response to first line crizotinib and primary resistance to subsequent ceritinib, while no known genetic resistance mechanism was identified and other mechanisms including histologic transformation were unlikely. Future research is needed to unveil the resistance mechanism and formulate effective treatment strategies.

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Current treatment and future challenges in ROS1- and ALK-rearranged advanced non-small cell lung cancer

Cited by 50 publications

References 97 publications

Prognosis of lung cancer with simple brain metastasis patients and establishment of survival prediction models: a study based on real events

Prognosis of lung cancer with simple brain metastasis patients and establishment of survival prediction models: a study based on real events

Cancer Therapy Guided by Mutation Tests: Current Status and Perspectives

Case Report: Short-Term Response to First-Line Crizotinib Monotherapy in a Metastatic Lung Adenocarcinoma Patient Harboring a Novel TPR-ROS1 Fusion

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