Therapy for Stage IV Non–Small-Cell Lung Cancer With Driver Alterations: ASCO and OH (CCO) Joint Guideline Update

Abstract

PURPOSE To provide evidence-based recommendations updating the 2017 ASCO guideline on systemic therapy for patients with stage IV non–small-cell lung cancer (NSCLC) with driver alterations. A guideline update for systemic therapy for patients with stage IV NSCLC without driver alterations was published separately. METHODS The American Society of Clinical Oncology and Ontario Health (Cancer Care Ontario) NSCLC Expert Panel updated recommendations based on a systematic review of randomized controlled trials (RCTs) from December 2015 to January 2020 and meeting abstracts from ASCO 2020. RESULTS This guideline update reflects changes in evidence since the previous update. Twenty-seven RCTs, 26 observational studies, and one meta-analysis provide the evidence base (total 54). Outcomes of interest included efficacy and safety. Additional literature suggested by the Expert Panel is discussed. RECOMMENDATIONS All patients with nonsquamous NSCLC should have the results of testing for potentially targetable mutations (alterations) before implementing therapy for advanced lung cancer, regardless of smoking status recommendations, when possible, following other existing high-quality testing guidelines. Most patients should receive targeted therapy for these alterations: Targeted therapies against ROS-1 fusions, BRAF V600e mutations, RET fusions, MET exon 14 skipping mutations, and NTRK fusions should be offered to patients, either as initial or second-line therapy when not given in the first-line setting. New or revised recommendations include the following: Osimertinib is the optimal first-line treatment for patients with activating epidermal growth factor receptor mutations (exon 19 deletion, exon 21 L858R, and exon 20 T790M); alectinib or brigatinib is the optimal first-line treatment for patients with anaplastic lymphoma kinase fusions. For the first time, to our knowledge, the guideline includes recommendations regarding RET, MET, and NTRK alterations. Chemotherapy is still an option at most stages. Additional information is available at www.asco.org/thoracic-cancer-guidelines .

Lazertinib: First Approval

“…Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) have been the standard of care for patients with non-small cell lung cancer (NSCLC) harbouring EGFR activating mutations [e.g. exon 19 deletions (Ex19del) or exon 21 L858R point mutation] [ 1 – 3 ]. However, most patients receiving EGFR-TKIs eventually develop resistance to first-generation (gefitinib, erlotinib) or second-generation (afatinib, dacomitinib) drugs.…”

Stage IV ALK-Positive Lung Adenocarcinoma: 7.5-Year Complete Remission with Crizotinib

“…As mentioned in the introduction, current evidence shows that new agents like alectinib, brigatinib and lorlatinib are preferred firstline options for ALK-positive NSCLC, with superior efficacity and lower toxicity compared to crizotinib [14]. However, in a patient who was first started on crizotinib, the recommendation is still for the therapy to be continued as long as there is a clinical benefit.…”

Lung Cancer in Belgium

“…This will change with the further implementation of reference centers for orphan and lowprevalent diseases. 52 Thoracic oncologists mainly follow the European Society of Medical Oncology 34,[53][54][55][56] or the American Society of Clinical Oncology guidelines 57,58 and, to a lesser extent, KCE recommendations. 59 Most systemic therapies and indications proposed in the European Society of Medical Oncology guidelines are available in Belgium, with a few exceptions (Supplementary Table 2).…”