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Case history

Image not available. A 65-year-old man presented with a 6 week history of cough, fatigue, progressive breathlessness and significant weight loss. He had a 5 pack-year smoking history and had been a non-smoker since his 20s. He had no significant medical history and up to this point had been fit and well. Eastern Cooperative Oncology Group performance status was 0–1 and Medical Research Council dyspnoea score was 2.

Chest X-ray showed meniscal opacification at the left base (Figure 10.1). A subsequent CT scan demonstrated a left-sided pleural effusion with smooth pleural enhancement and a small peripheral pulmonary nodule. Small bilateral lung nodules were noted, and the possibility of early lymphangitis was raised (Figure 10.2). Video-assisted thoracoscopy pleural biopsy revealed a stage IV TTF1-positive lung adenocarcinoma.

Gene profiling demonstrated no evidence of ALK translocation or EGFR mutation. Programmed death-ligand 1 (PD-L1) staining was seen in 100% of the tumour cells at immunohistochemistry.

The patient was initiated on first line pembrolizumab. After three cycles, restaging CT showed improvement of the pleural thickening but progressive ground glass changes and pulmonary nodularity. A diagnosis of grade 1 pneumonitis was made and pembrolizumab was withheld.

The patient was re-challenged with pembrolizumab 6 weeks later but after two further treatments he presented acutely with increasing breathlessness and hypoxia. He was diagnosed with worsening grade 2 pneumonitis (Figure 10.3, chest X-ray; Figure 10.4, CT scan), which was treated promptly by cessation of pembrolizumab and initiation of high-dose oral steroids (1 mg/kg per day). This caused resolution of some of the CT changes and the patient improved clinically.

Given the severity of his pneumonitis, pembrolizumab was permanently discontinued and cancer therapy was changed to cisplatin and pemetrexed chemotherapy. Oral steroids were weaned.

What is the evidence supporting pembrolizumab use in this setting?

What is the differential diagnosis?

How should the patient be investigated?

Does the radiology support the diagnosis of pneumonitis?

How should the patient be managed?

Figure 10.1

Chest radiograph on presentation.

Figure 10.2

Lung windows from staging CT scan performed at time of diagnosis of stage IV NSCLC.

Figure 10.3

Chest radiograph at time of presentation with acute dyspnoea following re-challenge with pembrolizumab.

Figure 10.4

Lung windows from urgent CT pulmonary angiogram at time of presentation with acute dyspnoea following re-challenge with pembrolizumab.

What is the evidence supporting pembrolizumab use in this setting?

The Study of Pembrolizumab Compared to Platinum-Based Chemotherapies in Participants with Metastatic Non-Small Cell Lung Cancer (KEYNOTE-024) randomized 305 patients with non-small-cell lung carcinoma (NSCLC) who had not yet received systemic therapy ...

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