Testing and Recommendations: EGFR-Mutated Stage IV NSCLC

Charu Aggarwal, MD, MPH:I do recommend molecular testing for patients with non­­—small cell lung cancer. This is especially true for patients with nonsquamous histology as there are mutations that are therapeutically targetable, as well as potentially actionable. While there are phenotypes clinically that we can say may have a mutation, for example, Asians, women, or never smokers in general have a higher likelihood of mutations, we must continue to test or increase our probability of finding these patients. In addition, theKRASmutation is now increasingly becoming therapeutically targetable, so we must continue to look for these actionable and targetable mutations.

For my particular patient, the initial biopsy yielded insufficient tissue for molecular testing. Unfortunately, this is a scenario that is not uncommon. We find that about 25% to 35% of the time, tissue biopsies are insufficient for molecular testing due to the quality of the quantity of DNA that’s present in these samples.

At our center, we follow a protocol of reflex testing and we complement it with the use of plasma-based testing at the discretion of medical oncologists. Any time a sample is signed off as the non­—small cell lung cancer, it is automatically reflexed to test for PL-D1. If it is a nonsquamous specimen it automatically gets reflexed for gene sequencing on the tissue. When we see the patient in medical oncology, if there is a high clinical suspicion for an actionable mutation, I will often send off plasma NGS [next-generation sequencing] to increase my yield.

We have found that communication is key when we collaborate on the resulting process, especially as it relates to solid tumor gene sequencing. I will often communicate both with my proceduralist, who may be [an] interventional radiologist, or interventional pulmonologist, in terms of optimizing the yield of tissue. I will often also communicate with my molecular pathologist and my anatomic pathologist to ensure that the appropriate testing is being performed on each sample.

Plasma NGS is an invaluable tool that we currently use in our medical oncology practices. We conducted a study at the University of Pennsylvania where we enrolled about 323 patients with advanced non—small cell lung cancer. And we found that by incorporating plasma-based gene sequencing we were able to detect additional patients that may benefit from targeted therapy. This rate increased from about 20.5% with tissue alone to about 38% with the incorporation of plasma. We also found that plasma NGS was feasible. It was relatively easy to use and did not subject the patients to another biopsy.

I often say that if a mutation is found on plasma NGS, that we must act on it. However, the lack of a mutation doesn’t mean that it is a true negative as there may be cases and circumstances where patients may not be shedding enough circulating cell-free DNA. I always say that if there is a high clinical suspicion, that we must wait for tissue biopsy as that still remains our gold standard.

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