Canadian Consensus Recommendations on the Management of MET-Altered NSCLC

Abstract

In Canada, the therapeutic management of patients with advanced non-small cell lung cancer (NSCLC) with rare actionable mutations differs between provinces, territories, and individual centres based on access to molecular testing and funded treatments. These variations, together with the emergence of several novel mesenchymal-epithelial transition (MET) factor-targeted therapies for the treatment of NSCLC, warrant the development of evidence-based consensus recommendations for the use of these agents. A Canadian expert panel was convened to define key clinical questions, review evidence, discuss practice recommendations and reach consensus on the treatment of advanced MET-altered NSCLC. Questions addressed by the panel include: 1. How should the patients most likely to benefit from MET-targeted therapies be identified? 2. What are the preferred first-line and subsequent therapies for patients with MET exon 14 skipping mutations? 3. What are the preferred first-line and subsequent therapies for advanced NSCLC patients with de novo MET amplification? 4. What is the preferred therapy for patients with advanced epidermal growth factor receptor (EGFR)-mutated NSCLC with acquired MET amplification progressing on EGFR inhibitors? 5. What are the potential strategies for overcoming resistance to MET inhibitors? Answers to these questions, along with the consensus recommendations herein, will help streamline the management of MET-altered NSCLC in routine practice, assist clinicians in therapeutic decision-making, and help ensure optimal outcomes for NSCLC patients with MET alterations.

Tumor Biomarker Testing for Metastatic Colorectal Cancer: a Canadian Consensus Practice Guideline

“… 169 Thus, testing workflow and procedures should be optimized to ensure that molecular biomarker testing results be reported to the oncologist by the time of the first consultation. Guidelines from international pathology associations and Canadian consensus publications recommend a maximum of 10 working days from sample receipt by the testing laboratory to generation of a summary report, with the report being sent to the referring oncologist within 24 h. 6 , 8 , 170 – 172 For samples requiring send-out to a reference lab, the suggested turnaround time from specimen acquisition to arrival in the reference lab is three working days. 172 Hospital systems should perform internal quality assurance assessments to evaluate whether turnaround time benchmarks are met.…”

“…Guidelines from international pathology associations and Canadian consensus publications recommend a maximum of 10 working days from sample receipt by the testing laboratory to generation of a summary report, with the report being sent to the referring oncologist within 24 h. 6 , 8 , 170 – 172 For samples requiring send-out to a reference lab, the suggested turnaround time from specimen acquisition to arrival in the reference lab is three working days. 172 Hospital systems should perform internal quality assurance assessments to evaluate whether turnaround time benchmarks are met. In cases where benchmarks are not met, strategies to improve turnaround time should be considered, which may include reflexive testing for all new CRC diagnoses, adjustments to workflow, and/or implementation of rapid biomarker testing methods.…”

Consensus Recommendations for the Diagnosis, Biomarker Testing, and Clinical Management of Advanced or Metastatic Non-small Cell Lung Cancer With Mesenchymal-Epithelial Transition Exon 14 Skipping Mutations in the Middle East, Africa, and Russia

“…The NGS can be a DNA-based or RNA-based assay. The DNA-based assay detects genomic variant alterations and ablation of splicing sites, whereas RNA-based assays involve RNA transcript analysis that facilitates the identification of altered splicing and exon 13-15 fusion [ 9 , 27 ]. Numerous RNA splice variants are generated as part of METex14 skipping mutation that may not be captured by the DNA-based assays.…”

“…In contrast, the loss of exon 14 transcription can be directly identified by the NGS RNA sequencing platform making it one of the most conclusive detecting methods [ 44 ]. In addition, poor sensitivity is a concern for DNA-based amplicon NGS panels used in detecting METex14 skipping mutations, which can be overcome by RNA-based assays [ 9 ]. Hence, DNA-based hybrid-capture or amplicon-based NGS assay should be combined or used along with an RNA-based NGS panel [ 9 , 27 ].…”

“…Non-small cell lung cancer (NSCLC) is the most common type of lung cancer constituting around 85% of all lung cancers [ 7 ]. It is a debilitating subtype of lung cancer and is the prominent cause of death associated with cancer [ 8 , 9 ]. Several oncogenic driver gene mutations, including epidermal growth factor receptor (EGFR), Kirsten rat sarcoma viral oncogene homolog (KRAS), anaplastic lymphoma kinase (ALK), mesenchymal-epithelial transition (MET), c-ROS oncogene 1 (ROS1), and rearranged during transfection (RET) are known to play an essential role in the development of NSCLC [ 10 ].…”