Treatment Options: Newly Diagnosed EGFR+ NSCLC

Charu Aggarwal, MD, MPH:I am often asked by patients who have anEGFR-mutant lung cancer, “What are my treatment choices, and is immunotherapy an option?” I often talk to patients that this is a situation where we can truly use personalized medicine, and use a precise TKI [tyrosine kinase inhibitor] that can target the driver mutation for their cancer.

I talk to my patient about using osimertinib, not only for the progression-free survival advantage but for better tolerability, for the survival advantage, as well as for the improved intracranial response to treatment.

I also counsel my patient that there is…no clinical trial that shows that immunotherapy is beneficial for patients with these mutations. One clinical trial that showed that patients withEGFR-mutant non­—small-cell lung cancer may in fact not benefit from immunotherapy. Additionally, there is accumulating evidence that if we start with immunotherapy first for patients withEGFR-mutant non­—small-cell lung cancer, that there may be a higher rate for immunotherapy-related adverse events after a TKI is introduced.

We recently saw overall survival data from the FLAURA trial. Previously we had seen progression-free survival improvement with the use of osimertinib in the frontline setting for metastatic non—small-cell lung cancer. The use of osimertinib was associated, associated with a progression-free survival of 18.9 months compared with 10.2 months with the use of erlotinib or gefitinib.

Most recently, we saw that osimertinib was associated with an improvement in overall survival with a median overall survival of 38.6 months, which for the first time is the first trial to show an overall survival advantage with the use of EGFR TKI in the frontline setting. This was also associated with higher and superior tolerability with this drug.

The final results from the FLAURA trial were recently presented and subsequently published in theNew England Journal of Medicine. Two years ago we had seen the progression-free survival data where osimertinib in the frontline setting for patients withEGFR-mutant non—small cell lung cancer improved, showed improved outcomes compared with first-line erlotinib or gefitinib.

We saw progression-free survival of about 18.9 months compared with about roughly 10 months with the use of other TKIs. Based on that information we had begun to use first-line osimertinib based on the superior tolerability and the significant improvement in progression-free survival.

Most recently, we saw overall survival data with the use of osimertinib, and the results confirmed a survival benefit. Not only that, the final analysis continued to show an improvement in CNS [central nervous system] penetration as well as superior tolerability. This is the first time that a TKI has been shown to improve overall survival in the frontline setting. Therefore, I have been using it as my first-line option, and the recent data further consolidate my approach.

Transcript edited for clarity.

Case: A 64-Year-Old Male with Untreated Stage IVEGFRMutated NSCLC

Initial presentation

• A 64-year—old man presented with shortness of breath, productive cough, chest pain, fatigue, anorexia and an 8-lb weight loss.
• PMH: HTN, medically controlled
• SH: non-smoker, social alcohol use
• PE: tired-appearing man, decreased breath sounds on auscultation

Clinical workup

• Imaging:
  • Chest x-ray showed a left lower lobe mass  
  • Chest/abdomen/pelvic CT scan confirmed a node extension, a 4.7-cm left lower lobe mass with mediastinal and hilar lymphadenopathy; left-sided adrenal metastases noted
  • PET scan showed activity in the left lower lobe mass and hilar nodal areas
  • Brain MRI showed no evidence of metastases
• Staging: T3N3M1a - IVA adenocarcinoma; ECOG PS 1
• Bronchoscopy with transbronchial biopsy of the left lower lobe was minimal and insufficient, subsequent plasma testing showedEGFRexon 19 deletion mutation

Treatment

• Patient was started on osimertinib 80 mg PO qDay
  • At 3-week follow-up the patient had been tolerating treatment well; continued on therapy
• Repeat Imaging at 3 months showed partial response
• Follow-up at 6 and 9 months showed stable disease
• At 18-months, CT scan revealed a new solitary liver lesion