Treatment of EGFR+ NSCLC After Progression

Charu Aggarwal, MD, MPH:My patient responded quite well, tolerated the drug very well, and continued to show a response at subsequent scans after the first restaging scan had been performed at 3 months.

Unfortunately, we saw isolated progression at 18 months. I would say this is not surprising. We have seen on clinical trials that the progression-free survival on osimertinib is about 18.2 months. This patient’s progression happened right about that time. I’m not surprised that this happened.

At the time of progression, I often re-biopsy to confirm progression and also to determine what the histology is at the time of the progressing event. I usually proceed with restaging scans in the form of CT scans of the chest, abdomen, and pelvis, as well as an MRI of the brain, and then proceed based on the results.

We made a lot of progress to date in the treatment of non-small cell lung cancer, especially for patients withEGFR-mutant disease. We are routinely looking for these mutations. We now have better drugs that can provide superior survival outcomes with better penetration into the brain. I would say that there are still areas that we can do better in, one of which is the use of plasma-based next-generation sequencing, not just at diagnosis but also to follow patients and to really identify patients who may not be deriving the full benefit from frontline therapy. Additional areas of research include treatment at the time of progression, what to do once osimertinib stops working.

We now know that meta-amplification is the mechanism for a majority of the patients that progress on osimertinib, and clinical trials are underway to evaluate drugs that may target that amplification. So much more to come and this is an exciting time.

Transcipt 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