TARGET for NSCLC: The Advancing Research into Genomic Pathways and use of EGFR Therapies

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Post-test Question #1:

Patricia is a 58-year-old female former smoker (5 pack-year). She presents with new-onset shortness of breath. Her ECOG performance status is 1. A chest X-ray shows large right sided pleural effusion. A chest CT shows a right upper lobe mass with associated ipsilateral hilar and paratracheal adenopathy and large ipsilateral pleural effusion. Pleural fluid cytology shows adenocarcinoma cells, TTF1+, and p40 –. PET/CT demonstrates metastases to the liver and bone. MRI of the brain with/without contrast shows no brain metastases.

What is the best next step using a cell block prepared from the pleural fluid? *

Perform single-gene testing for KRAS mutation and PD-L1 immunohistochemistry testing; if negative for KRAS, do reflex testing for EGFR and ALK

Perform a broad-based next-generation sequencing (NGS) panel with reflex RNA testing plus PD-L1 immunohistochemistry

Perform single-gene testing for EGFR mutations, BRAF V600E mutations, and MET exon 14 skipping mutations, plus fusion testing for ALK, ROS1, RET, and NTRK fusions

Perform PD-L1 testing by immunohistochemistry and simultaneous single-gene tests for EGFR mutations, ALK fusions, KRAS mutations, and ROS1 fusions

Post-test Question #2:

Pauline is a 38-year-old female recently diagnosed with NSCLC harboring an EGFR exon 19 deletion. Brain MRI shows 7 brain metastases; the largest is 1.8 cm; the brainstem is not involved, and there is minimal vasogenic edema.

What is the best next step? *

Start osimertinib 80 mg/day

Consult radiation oncology for STAT whole brain radiation therapy

Consult neurosurgery

Start erlotinib 150 mg/day

Post-test Question #3:

James is a 55-year-old male with stage IV NSCLC (adenocarcinoma, PD-L1 TPS=80%, harboring an EGFR exon 19 deletion) treated with osimertinib for the past 18 months. He has an ECOG performance score of 0 and has tolerated treatment well with no side effects. He was last seen 3 months ago when he presented with worsening bone pain and weight loss. An MRI of the brain revealed no evidence of CNS metastases. CT C/A/P with contrast reveals liver and bone metastases; a biopsy of the liver lesion reveals adenocarcinoma with high level MET amplification (MET/CEP7 ratio = 10).

Which of the following is the most reasonable treatment approach? *

Continue osimertinib and add a MET inhibitor

Start pembrolizumab monotherapy since PD-L1 was 80%

Start carboplatin plus paclitaxel plus pembrolizumab

Switch to capmatinib (MET inhibitor) as monotherapy

Post-test Question #4:

Donald is a 71-year-old former heavy smoker who presents with worsening shortness of breath. He is found to have lung adenocarcinoma also involving the lymph nodes, bone, and liver. Molecular testing revealed an EGFR exon 20 insertion mutation.

Which of the following is NOT an FDA-approved second-line therapy option for this molecular subtype? *

Osimertinib

Amivantamab-vmjw

Mobocertinib

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TARGET for NSCLC: The Advancing Research into Genomic Pathways and use of EGFR Therapies