Non–small-cell lung cancer (NSCLC) treatment has changed in recent years with the development of therapies that target the genetic mutations driving cancer proliferation. Biomarker testing is recommended in patients with advanced NSCLC with an adenocarcinoma component for genetic mutations in EGFR, ALK, ROS1, BRAF, NTRK1/2/3, MET exon 14 skipping, and RET to tailor treatment. In addition, for younger patients and for those without a history of exposure to tobacco without adenocarcinoma, molecular testing is also recommended. For those patients with stage I-III NSCLC, guidelines have only recently recommended molecular testing. Standard of care for this patient population is surgery with or without chemotherapy/chemoradiotherapy. A meta-analysis of 115,815 patients with NSCLC found that the presence of the EGFR mutation is as prevalent in patients with stage I-III NSCLC as with advanced NSCLC.
The ADAURA clinical trial evaluated the use of osimertinib, an EGFR tyrosine kinase inhibitor, in patients with completely resected EGFR-mutation–positive stage IB to IIIA NSCLC compared with placebo for 3 years.1 The patients who received osimertinib had significantly longer disease-free survival than those who received placebo.1 These results led the FDA to approve osimertinib as adjuvant treatment in patients with resected Ex19del or L858R EGFR-mutated NSCLC. There are multiple ongoing clinical trials with other targeted agents in this patient population. Considering these developments, a review of integrating molecular testing into the management of stage I-III NSCLC was presented in the journal Lung Cancer.
Molecular testing of either biopsy or resection samples is strongly preferred over on-demand testing and should be written into guidelines for stage I-III NSCLC disease management protocols. At initial diagnosis, tumor heterogeneity is generally not an issue for EGFR testing but avoiding areas with high inflammatory cell counts or high stromal cell content is advised. The suggested minimum number of cells for molecular testing is 100 to 400 tumor cells, but with <300 tumor cells there is an increased chance of artifact interference. At this time, liquid biopsy is not sensitive enough to recommend in early-stage disease. Comprehensive molecular testing including all targetable mutations is advised not only to direct treatment, but also to determine eligibility for clinical trials and to guide later treatment decisions. However, insurance reimbursement will need to be considered when making this decision. A testing strategy involving a multidisciplinary team approach to coordinate testing and reflex molecular testing has the potential to capture patients at early disease stages by avoiding diagnostic delays and reducing unnecessary testing.
With the development of new, targeted therapies well underway in clinical trials for stage I-III NSCLC, comprehensive molecular testing will become an important component of comprehensive care.
Source
Aggarwal C, Bubendorf L, Cooper WA, et al. Molecular testing in stage I-III non-small cell lung cancer: approaches and challenges. Lung Cancer. 2021;162:42-53.
Reference
- Wu YL, Tsuboi M, He J, et al. Osimertinib in resected EGFR-mutated non-small-cell lung cancer. N Engl J Med. 2020;383:1711-1723.
