A collaborative effort between the American Society of Clinical Oncology (ASCO) and Ontario Health (OH) has updated the Joint Guideline on Therapy for Stage IV Non-Small-Cell Lung Cancer With Driver Alterations for the first time since 2017.  

The current update includes targeted therapy for NSCLC patients with driver alterations in epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), proto-oncogene receptor tyrosine kinase (ROS1), BRAF V600e mutations, RET fusions, MET exon 14 skipping mutations, and NTRK fusions (with known marker status test results available to the clinician). 

According to expert panel co-chairs Nasser H. Hanna, MD, and Gregory Masters, MD, all patients with nonsquamous NSCLC should first undergo testing for potentially targetable mutations prior to implementing therapy for advanced lung cancer, regardless of smoking status recommendations.  

The majority of patients should receive targeted therapy for these alterations, either as initial or second-line therapy when not given in the first-line setting. 

In patients with driver alterations in EGFR, those with T790M, L858R, or exon 19 deletion mutations should receive osimertinib as first-line therapy.  

If osimertinib is not available, either gefitinib with chemotherapy or dacomitinib are recommended. Other second-line options include afatinib, erlotinib/bevacizumab, erlotinib/ramucirumab, gefitinib, erlotinib, or icotinib. 

Among individuals with driver alterations in ALK, the recommended first-line treatment is alectinib or brigatinib. If these agents are not available in the first-line setting, then ceritinib or crizotinib will suffice.  

If alectinib or brigatinib was a first-line therapy, lorlatinib is recommended as second-line therapy.  

If patients received first-line crizotinib, then alectinib, brigatinib, or ceritinib should follow. 

In patients with ROS1 driver alterations, crizotinib or entrectinib are recommended first-line agents. 

If a ROS1-targeted therapy was administered as first-line therapy to these patients, standard treatment based on the ASCO/OH nondriver mutation guideline is recommended as second-line therapy. 

Among patients with RET driver alterations, either selpercatinib, standard treatment based on the ASCO/OH nondriver mutation guideline, or pralsetinib (pending confirmatory data) may be offered as first-line treatment. 

Finally, the guideline addressed patients with driver alterations in NTRK, recommending first-line treatment with entrectinib or larotrectinib, or standard treatment based on the ASCO/OH nondriver mutation guideline.  

If NTRK-targeted therapy was administered as first-line treatment, standard treatment based on the ASCO/OH nondriver mutation guideline may be offered as second-line therapy. 

“In just a very short number of years since 2017 we’ve made tremendous progress. We have at least three new targets and many new treatments for almost every class of targeted therapy indication in lung cancer. Most of these targets are oral therapies, and many of them should now be offered to patients as first- or second-line treatment instead of chemotherapy. So for patients, this really means many more will be able to enjoy a chemotherapy-free world or at least a chemotherapy-free period for a time,” guideline co-author Natasha B. Leighl, MD, said in an associated podcast. 


By Michael Vlessides, /alert Contributor