Impressions of a Woman With EGFR+ Metastatic NSCLC

Edgardo Santos Castillero, MD, FACP:This case is about a 63-year-old woman patient who, unfortunately, was diagnosed with metastatic non—small cell lung cancer [adenocarcinoma histology type]. This patient during work-up was found to have, as I mentioned before, metastatic disease. Molecular testing was performed in the biopsy, showing that the patient had anEGFR[epidermal growth factor receptor] exon 21 mutation known as L858R, and a PD-L1 [programmed death-ligand 1] expression of 14%. Other biomarkers that were also studied were negative. The patient was found not to have any brain metastases and had a good performance status.

My first impression of this case is that we have a lady who has a very good performance status, which is the most important thing we want to know before we decide what kind of therapy we are going to offer the patient. Then the case was very well analyzed. Molecular testing was performed, and we have been able to identify a driver mutation known asEGFRexon 21 L858R.

When we have a patient like this, we would certainly like to start with targeted therapy. Following the National Comprehensive Cancer Network Guidelines, there are several kinds of medications, known as tyrosine kinase inhibitors [TKIs], that we can offer the patient.

We have several agents. Today the preferred agent for this patient is osimertinib, because this agent has shown overall survival in comparison with other TKIs. There was a study called the FLAURA study that showed that osimertinib was superior to a first-generation TKI. However, a new study called the RELAY study combining erlotinib plus ramucirumab, which is an antibody against vascular endothelial growth factor receptor 2, recently showed a very impressive progression-free survival. The trial has very good outcomes, specifically for the patients who is in discussion—those patients who have exon 21 L858R genomic abnormality.

Those patients who have anEGFRmutation or any kind of driver mutation do much better than patients who do not have this mutation. Certainly, those patients will have the option to receive targeted therapy, which will attack that particular genomic abnormality to move the progression of the tumor. And then they also will have a chance to go down the line to receive other kinds of therapy, such as immunotherapy, in combination with chemotherapy or other agents. Moreover, with some of this targeted therapy we are also discovering mechanisms of resistance, for which, in some cases, we have medication against resistance. In other cases, we continue doing research to try to identify new agents so we can provide this kind of therapy for these patients who, in particular, haveEGFRmutations.

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

Treatment

• 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