Future Directions in EGFR+ NSCLC

Edgardo Santos Castillero, MD, FACP:For many years, we have used TKIs [tyrosine kinase inhibitors] based on progression-free survival. All the agents, since 2008, have been approved by regulatory entities based on progression-free survival. It was not until recently—a few years ago—that the ARCHER 1050 study also proved overall survival. Although that TKI—dacomitinib—has a bit more toxicity than other TKIs.

We were waiting for the FLAURA study, because in that study osimertinib, a third-generation TKI, was compared with either erlotinib or gefitinib. The toxicity profile of osimertinib is more compelling for the patient, and its story shows overall survival. Based on that publication of the FLAURA study last year, osimertinib became the preferred agent. We’re using our guidelines to help make treatment decisions, but there is 1 that goes above all them, which is osimertinib.

Now we have this new study combining erlotinib with a VEGF inhibitor, ramucirumab, again making an outcome in terms of progression-free survival—19.4 months—which is very good. But the problem is that it’s 2 drugs. When we have 2 drugs and we compare against osimertinib monotherapy, the progression-free survival by itself is 18.4 months. So we don’t like to compare clinical trials against clinical trials, but those are the numbers. What are we going to use, monotherapy or dual therapy?

When we go deep into the RELAY study, the efficacy for theEGFRexon 21 mutation caught our attention. Through all the studies that have been developed forEGFRmutations, we know that exon 21 is not exon 18, which is more sensitive. Both of them will respond to a TKI; however, that response that we have obtained for exon 21 never has been as good as exon 18. So we know that there are differences among theEGFRmutations.

This combination came as another option. It’s category 2A by the National Comprehensive Cancer Network. It’s made us aware that these particular agents, known as vascular endothelial growth factor inhibitors, can be combined with EGFR and can also add more to the EGFR.

One other thing we are waiting on is results of the ongoing clinical trial combining osimertinib plus ramucirumab. We expect to see more changes in the landscape of treating patients withEGFRmutations very soon.

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