Interactive Case Challenge - EGFRm NSCLC Progression on Osimertinib

For those who practice in academic or community settings, please indicate your practice setting:

A.
Academic
B.
Community
C.
Not applicable

How many people with non-small-cell lung cancer (NSCLC) do you provide care for in a typical month?

A.
1-4
B.
5-10
C.
11-15
D.
16-20
E.
>20
F.
Not applicable

Your patient has metastatic EGFR exon 19–mutated NSCLC. She received first-line osimertinib and then local therapy for isolated progression while continuing osimertinib, followed by carboplatin/pemetrexed plus ongoing osimertinib for later systemic progression. She now has renewed systemic progression with stable central nervous system (CNS) disease.

Which of the following treatment options would you recommend for this patient based on available evidence and current approved indications?

A.
Amivantamab with lazertinib
B.
Datopotamab deruxtecan (Dato-DXd)
C.
Pembrolizumab monotherapy
D.
Docetaxel

A patient with metastatic EGFR-mutated NSCLC has started Dato-DXd. After 2 cycles, she reports mild mouth soreness. On examination, she has erythema without ulcers, consistent with grade 1 oral mucositis/stomatitis, but she is still eating and drinking normally.

Which of the following management strategies would you recommend as the best next step in her care now?

A.
Hold Dato-DXd until the stomatitis improves and restart at the same dose
B.
Hold Dato-DXd until the stomatitis improves and restart at a reduced dose
C.
Continue Dato-DXd and intensify oral supportive care
D.
Continue treatment and begin high-dose systemic corticosteroids

History
Your patient is a 58-year-old woman (never-smoker) with metastatic NSCLC (adenocarcinoma) harboring an EGFR exon 19 deletion. At diagnosis 3 years ago, she had a symptomatic 1.8-cm right parietal brain metastasis, treated with stereotactic radiosurgery, and multiple bilateral pulmonary nodules with mediastinal adenopathy.

She started first-line osimertinib 80 mg orally once daily and achieved a durable partial response. She remains active (Eastern Cooperative Oncology Group performance status 1) and has had stable brain MRI surveillance.

Current Presentation
At today’s routine restaging visit, CT chest/abdomen/pelvis shows a new solitary 1.6-cm liver lesion. All other known sites are stable, and brain MRI remains without new or progressive disease. She is asymptomatic and asks, “Do I need to change treatment now?”

Which approach would you recommend as best option for this patient at this time?

A .
Order plasma circulating tumor DNA (ctDNA) and decide next therapy based on that result

11.7%
B .
Biopsy the new liver lesion (tissue) to evaluate resistance and histology

57.7%
C .
Treat the new lesion with local therapy now, without obtaining any biopsy

18.9%
D .
Stop osimertinib and begin platinum-based chemotherapy immediately

11.7%

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Management of a Patient With EGFR-Mutated NSCLC and Progression on First-line Osimertinib

Helena Yu, MD

Activity

For those who practice in academic or community settings, please indicate your practice setting:

How many people with non-small-cell lung cancer (NSCLC) do you provide care for in a typical month?

Which approach would you recommend as best option for this patient at this time?