EGFR-VEGF Inhibition for First-Line EGFR+ mNSCLC Treatment

Edgardo Santos Castillero, MD, FACP:That RELAY study that has been presented recently is a study that combined erlotinib, a first-generation TKI [tyrosine kinase inhibitor], plus ramucirumab, which is an antibody against vascular endothelial growth factor receptor 2, an antiangiogenic agent. That combination was compared against erlotinib. This study had a primary end point of progression-free survival and was positive. This is a study of progression-free survival of 19.4 months.

What is more striking in this particular study is the fact that progression-free survival forEGFR[epidermal growth factor receptor] exon 21 was also 19.4 months. If we look at all the studies that have been published since the first TKI was approved by the regulatory entities, we have not found a longest progression-free survival in this particular group—EGFRexon 21 L858R—until that RELAY study. In this case, this particular combination may induce a great outcome in this population. Overall survival from the RELAY study is immature, so we cannot make any comment regarding overall survival.

The particular case that we presented today is about a 63-year-old Caucasian woman with stage IV disease with anEGFRmutation, in particular L858R genomic abnormality, with a PD-L1 [programmed death-ligand 1] expression of 14%, a good performance status, and no brain lesions. This is a patient who basically is a classic, eligible participant for the RELAY study. The physician may consider the combination of erlotinib plus ramucirumab based on the profile of this particular case.

When we combine an EGFR inhibitor with a VEGF inhibitor, we will see toxicity. Most toxicity is low in grade—grade 1 to grade 2. In the particular case of the RELAY study, the most common adverse event in terms of grade 3 was hypertension, which basically goes with the adverse effect seen with the use of particular drugs, such as ramucirumab. This medication that inhibits VEGF has its own adverse effects—hypertension, proteinuria, wound-healing effects, and things like that. But in particular, on this combination, the thing that was most seen was hypertension. Also, we found that the acneiform rash from erlotinib was a little more pronounced in terms of incidence. But this medication has been on the market for years already, so we know how to handle this kind of common toxicity when we combine these medications.

Also, I would like to mention that in the RELAY study, as well as other studies that have combined EGFR and VEGF in the past, there is something really intriguing: the fact that interstitial lung disease, which is an adverse effect from the EGFR, has been seen in less incidence. There seems to be a protective effect of the VEGF inhibitor.

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