Current Molecular Testing Strategies for EGFR+ NSCLC

Edgardo Santos Castillero, MD, FACP:When we have a patient with non—small cell lung cancer, and specifically an adenocarcinoma histology type, molecular testing is mandatory. If we follow our guidelines, we test forEGFR[epidermal growth factor receptor],ALK,BRAF,NTRK, as well as PD-L1 [programmed death-ligand 1], andROS1. We have to do those kinds of testing.

Something that has become more standard is the use of next-generation sequencing. What is that? Basically, with a small piece of tumor we are able to study different genes. The panel can go from 50, 100, 200, depending on what laboratory we use. Next-generation sequencing will allow us to analyze the broad spectrum of this particular tumor, so we will be able to identify most of the targets that we now have in lung cancer.

The second part of the question here is, should we wait for the results? Yes, we should wait for the results, because No. 1, you want to give the patient the correct therapy and the best therapy at the beginning. Moreover, with the use of immunotherapy now in the frontline, we need to be very careful using immunotherapy right away without knowing if the patient has a driver mutation. There have been studies that have already been published showing that if we start a patient on immunotherapy, and we receive the results later on and the patient has, for example, anEGFRmutation—where we are trained to use the appropriate targeted therapy on those patients already exposed to immunotherapy—toxicity happens. We need to avoid that.

Transcript edited for clarity.

Case: A 63-Year-Old Woman With MetastaticEGFR+ NSCLC

Initial presentation

  • A 63-year-old woman presented with persistent cough, and a 5-lb weight loss
  • PMH/SH: former smoker, quit 25 years ago
  • PE: Decreased breath sounds on auscultation in the right lower lobe

Clinical workup

  • Labs: WNL
  • PFT: FEV1/FVC 60%; DLCO 68%
  • Chest X-ray showed a right lower lobe soft tissue mass
  • Chest/abdominal/pelvic CT showed a 3.8-cm solid pulmonary mass in the right lower lobe; enlarged contralateral hilar and mediastinal lymph nodes; 3 small right adrenal lesions noted
  • CT‐guided core needle biopsy of the lung mass revealed lung adenocarcinoma; lymph node biopsy showed grade 2 adenocarcinoma
  • Contrast‐enhanced MRI of the head showed no evidence of brain metastases
  • Molecular testing:EGFRexon 21 substitution L858R, ALK-, BRAF-, ROS1-, RET-, MET-, ERBB2-,PD-L1 TPS 14%
  • Staging- T2aN3M1b - IVA; ECOG PS 0


  • Patient was started on erlotinib 150 mg PO qDay + ramucirumab 10 mg/kg IV
    • Imaging at 3-month showed partial response with decrease in lung lesion
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