Improved Outcomes for Patients With EGFR+ NSCLC

John Heymach, MD, PhD:What is notable about the case, and what are my initial thoughts about the management? Well, this, in a lot of ways, is a typical patient with EGFR mutations. Now, EGFR mutations can happen in nonsmokers, of course, very frequently, but they happen in smokers as well. We often like to say, smoking doesn’t prevent you from getting an EGFR-mutant non–small cell lung cancer, and that’s important because sometimes smokers, or at least former smokers, are not being tested for all these mutations.

I think one important point is that patients, regardless of whether they’re a smoker or not, with lung adenocarcinoma or nonsquamous histology in general, should get molecular testing.

In general, I will test squamous cell carcinomas as well. First of all, sometimes the histology is not recognized as nonsquamous histology; sometimes there’s disagreement about the histology, and patients with squamous histology will sometimes have an EGFR mutation, or one of the other driver oncogenes.

When I started practicing thoracic oncology a little more than 2 decades ago, the outcome for somebody in this situation would have been a median overall survival of less than a year. In fact, it was on the order of 9 months or 10 months at that point. Fortunately, right now, for somebody [with] newly diagnosed…EGFR-mutant non–small cell lung cancer in this situation, the median expected overall survival is somewhere in the area of 40 months, and in fact that number is getting longer and longer as some of our better drugs now are being more wisely used, and we’re developing new tools to be added to the toolbox as well.

The treatment landscape for patients like this has really changed dramatically over the last 2 decades since I started practicing thoracic oncology. In the early 2000s, options for these patients would be really limited to platinum doublet chemotherapy, or a single-agent chemotherapy after that. And the median overall survival of patients in this situation was right around 8 months to 10 months.

If you look at studies like FLAURA and RELAY, the median overall survival is in the range of 38 months or even longer than that. We don’t even have a median overall survival yet for patients treated on the RELAY study. So, this really is remarkable progress. Just think about that, From 8 months to 10 months to now in the area of 40 months and getting longer. So that really is striking.

Now, that progress is coming for a couple of reasons. First of all, we’ve got targeted agents for use in the first-line setting–EGFR inhibitors most prominently for a patient with a typical EGFR mutation like this. …Patients who develop resistance to first- or second-generation EGFR inhibitors now get a third- generation inhibitor. Our chemotherapy regimens have gotten better with the addition of bevacizumab, platinum doublet chemotherapy. And now with the addition of immunotherapy, that can be used after platinum doublet, although immunotherapy doesn’t tend to be particularly effective for patients with an EGFR mutation, but it does remain an option. And for patients who are receiving second-line chemotherapy with agents like docetaxel, we have the addition of ramucirumab. So, if you add together all those changes cumulatively, for patients with EGFR-mutant non–small cell lung cancer, that amounts to dramatic improvements in the overall survival.

Transcript edited for clarity.

Case:A 68-Year-Old Man With Metastatic EGFR+ NSCLC

Initial presentation

• A 68-year-old man presented with recent onset shortness of breath and unintentional weight loss; he denies nausea, vomiting or headaches
• PMH: Hyperlipidemia controlled on a statin; former smoker, quit 10 years ago with a 30 pack-year history
• PE: Decreased breath sounds in left lower lung field on auscultation
  
  

Clinical workup

• Labs: WNL
• PFT: FEV1/FVC 55%; DLCO 65%
• Chest X-ray showed a left lower lobe soft tissue mass
• Chest/abdominal/pelvic CT showed a 3.3-cm solid pulmonary mass involving the left main bronchus and ipsilateral subcarinal lymph nodes, and adrenal metastases
• CT-guided core needle biopsy lung lesion and lymph nodes revealed grade 2 lung adenocarcinoma
• Contrast‐enhanced MRI of the brain was negative
• Molecular testing: EGFR exon 19 deletion, ALK-, ROS1-, BRAF-, PD-L1 TPS 20%
• Stage IVA – T2N2M1a; ECOG PS 1
  
  

Treatment

• Patient was started on erlotinib 150 mg PO qDay + ramucirumab 10 mg/kg IV q2weeks
  • Imaging at 3-month showed partial response with decrease size of lung and adrenal lesions
  • Imaging at 6-, 12- and 18-month follow-up showed stable disease