Treating NSCLC With Gene Mutations – Discussion with Dr. Gregory Masters

An interview with Dr. Gregory Masters discussing the latest guidelines treating non-small cell lung cancer (NSCLC) with gene mutations.

A year ago, ASCO released a clinical practice guideline on systemic therapy for patients with stage IV non-small cell lung cancer (NSCLC) without driver alterations. Part two has now been released, and it focuses on patients with stage IV NSCLC with driver alterations.

The guideline “is a result of potentially practice-changing evidence published since the last update [in 2017],” noted Gregory Masters, MD, of the ChristianaCare Helen F. Graham Cancer Center and Research Institute in Newark, Delaware, and colleagues.

The updated guideline offers 41 recommendations, including the following:

• Patients should be offered targeted therapies against ROS-1 fusions, BRAF V600e mutations, RET fusions, MET exon 14 skipping mutations, and NTRK fusions as first- or second-line therapy when not given in the first-line setting
• Osimertinib (Tagrisso) is the optimal first-line treatment for patients with activating EGFR mutations, such as exon 19 deletion, exon 21 L858R, and exon 20 T790M
• Alectinib (Alecensa) or brigatinib (Alunbrig) is the optimal first-line therapy for patients with ALK fusions
• Chemotherapy is still an option at most stages

“For the first time, to our knowledge, the guideline includes recommendations regarding RET, MET, and NTRK alterations,” the panel members noted.

For instance, stage IV NSCLC and MET exon 14 skipping mutation may be treated with MET-targeted therapy — capmatinib (Tabrecta) or tepotinib (Tepmetko) — in the first-line setting, while for patients with stage IV NSCLC and driver alterations in RET, first-line setting, selpercatinib (Retevmo) is an option.

In the following interview, Masters, the co-chair of the Expert Panel, who is also associate professor at Thomas Jefferson University Medical School in Philadelphia, offers more details on the guideline, which was produced along with Cancer Care Ontario in Canada.