Molecular Testing Guideline for the Selection of Patients With Lung Cancer for Treatment With Targeted Tyrosine Kinase Inhibitors: American Society of Clinical Oncology Endorsement of the College of American Pathologists/International Association for the Study of Lung Cancer/Association for Molecular Pathology Clinical Practice Guideline Update

Abstract

Purpose In response to advances in the field, the College of American Pathologists (CAP), the International Association for the Study of Lung Cancer (IASLC), and the Association for Molecular Pathology (AMP) recently updated their recommendations for molecular testing for the selection of patients with lung cancer for treatment with targeted tyrosine kinase inhibitors. ASCO has a policy and set of procedures for endorsing clinical practice guidelines that have been developed by other professional organizations. Methods The molecular testing guideline was reviewed for developmental rigor by methodologists. Then an ASCO Expert Panel reviewed the content and the recommendations. Results The ASCO Expert Panel determined that the recommendations from the CAP/IASLC/AMP molecular testing guideline are clear, thorough, and based upon the most relevant scientific evidence. ASCO endorsed the guideline with minor modifications. Recommendations This update clarifies that any sample with adequate cellularity and preservation may be tested and that analytical methods must be able to detect mutation in a sample with as little as 20% cancer cells. It strongly recommends against evaluating epidermal growth factor receptor (EGFR) expression by immunohistochemistry for selection of patients for EGFR-targeted therapy. New for 2018 are recommendations for stand-alone ROS1 testing with additional confirmation testing in all patients with advanced lung adenocarcinoma, and RET, ERBB2 (HER2), KRAS, and MET testing as part of larger panels. ASCO also recommends stand-alone BRAF testing in patients with advanced lung adenocarcinoma. Recommendations are also provided for testing methods for lung cancers that have a nonadenocarcinoma non-small-cell component, for patients with targetable mutations who have relapsed on targeted therapy, and for testing the presence of circulating cell-free DNA. Additional information is available at www.asco.org/thoracic-cancer-guidelines and www.asco.org/guidelineswiki .

Combined targeted DNA and RNA sequencing of advanced NSCLC in routine molecular diagnostics: Analysis of the first 3,000 Heidelberg cases

“…tyrosine kinase inhibitors (TKI) for EGFR and BRAF mutated or ALK-and ROS1-translocated tumors, which have facilitated survival rates twice as high as chemotherapy, 3 as well as the development of immune checkpoint inhibitors, which can induce long-term remissions in about 15-20% of metastatic cases. According to international guidelines for molecular testing of lung cancer as updated in 2018, [5][6][7][8] any lung cancer sample (tissue biopsy or cytology) with adenocarcinoma or not-otherwise specified (NOS) histology and adequate tumor cellularity should be tested for routinely treatable mutations with a turnaround time of no more than 10 working days. According to international guidelines for molecular testing of lung cancer as updated in 2018, [5][6][7][8] any lung cancer sample (tissue biopsy or cytology) with adenocarcinoma or not-otherwise specified (NOS) histology and adequate tumor cellularity should be tested for routinely treatable mutations with a turnaround time of no more than 10 working days.…”

<b><i>BRAF</i></b> Mutations in Lung Cancer

“…Indeed, in their updated guidelines, the College of American Pathologists (CAP), the International Association for the Study of Lung Cancer (IASLC), and the Association for Molecular Pathology (AMP) recommended BRAF molecular assessment when next-generation sequencing (NGS) panels are adopted [3]. Even more recently, the American Society of Clinical Oncology (ASCO) established that BRAF testing should be performed on all patients with advanced lung ADC, even outside clinical trials [4]. To this end, NGS enables researchers to detect all relevant BRAF mutations involving both exon 15 (codon 600) and exon 11 (codons 466 and 469) [2].…”

Timing of folic acid/vitamin B12 supplementation and hematologic toxicity during first‐line treatment of patients with nonsquamous non–small cell lung cancer using pemetrexed‐based chemotherapy: The PEMVITASTART randomized trial

“…Current research focuses on the integration of both of these newer “pillars” of treatment with conventional treatment modalities (ie, chemotherapy, radiation, and surgery) as precision medicine continues to be refined on an almost monthly basis . Nonetheless, chemotherapy remains the backbone of treatment for advanced/metastatic ns‐NSCLC, in which predictive molecular biomarkers for upfront targeted therapy (epidermal growth factor receptor [ EGFR ] and v‐Raf murine sarcoma viral oncogene homolog B1 [ BRAF ] mutations; anaplastic lymphoma kinase [ ALK ] and ROS proto‐oncogene 1 [ ROS1 ] rearrangements) and upfront immunotherapy (monoimmunotherapy) (programmed death ligand 1 [PD‐L1] expression ≥50%) either have not been assessed or are absent . In this context, pemetrexed is the preferred drug to be used as a component of platinum‐based doublet chemotherapy for patients with ns‐NSCLC .…”

“…1 Nonetheless, chemotherapy remains the backbone of treatment for advanced/metastatic ns-NS-CLC, in which predictive molecular biomarkers for upfront targeted therapy (epidermal growth factor receptor [EGFR ] and v-Raf murine sarcoma viral oncogene homolog B1 [BRAF ] mutations; anaplastic lymphoma kinase [ALK ] and ROS proto-oncogene 1 [ROS1 ] rearrangements) and upfront immunotherapy (monoimmunotherapy) (programmed death ligand 1 [PD-L1] expression ≥50%) either have not been assessed or are absent. 2,3 In this context, pemetrexed is the preferred drug to be used as a component of platinum-based doublet chemotherapy for patients with ns-NSCLC. 4 Cancer July 1, 2019 It is also the preferred chemotherapeutic agent for patients with malignant mesothelioma.…”