EGFR-TKIs in First-Line EGFR+ Metastatic NSCLC

Edgardo Santos Castillero, MD, FACP:Decisions to select the best therapy for a patient, specifically a patient with anEGFR[epidermal growth factor receptor] mutation, will be impacted by factors such as performance status, the presence or absence of brain metastases, whether the patient has any brain lesions, if the patient has symptoms or no symptoms, and certainly the kind of mutation the patient has—as well as the presence of any comorbid conditions, which is very important. If the patient has cardiac issues or any other disease, that may impact the patient down the line.

If the patient has anEGFRmutation as well as expression of PD-L1 [programmed death-ligand 1], it should not impact the decision to put the patient on targeted therapy with, in this case, any of the tyrosine kinase inhibitors [TKI] that are approved here in the United States—osimertinib, erlotinib, gefitinib, and others. The fact that the patient may also have expression of PD-L1 should not influence, whatsoever, the use of targeted therapy.

There is preclinical and clinical data that demonstrates that EGFR tyrosine kinase inhibitors work well with VEGF inhibitors. This could be agents such as ramucirumab or bevacizumab, and those have been studied in the past.

A study has shown that when we combine these 2 classes of agents, responses are better than just by using the TKI alone. At this moment, when we comment on the preferred agent among the TKIs, we know that osimertinib is the preferred agent. Right now, there are also studies ongoing combining osimertinib plus ramucirumab. Those results are really eagerly awaited by all of us.

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