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Case history

image A 69-year-old woman with an 8 week history of persistent cough and chest pain associated with a 2 kg weight loss was referred for urgent assessment. Investigations identified a 66 mm right upper lobe lung mass adjacent to the pleura with mediastinal and mesenteric lymphadenopathy and a sclerotic lesion at T3 vertebral body. Percutaneous CT-guided biopsy of the thoracic mass demonstrated a poorly differentiated TTF1-positive adenocarcinoma with features of sarcomatoid dedifferentiation. Her medical history included a hiatus hernia and type 2 diabetes mellitus. Her father had been diagnosed with lung cancer at the age of 66. She was a cleaner, married with two children and a smoker with an 80 pack-year history.

The thoracic multidisciplinary team recommended systemic therapy with palliative intent for pT3cN3cM1c non-small-cell lung carcinoma (NSCLC) adenocarcinoma subtype and she was referred to medical oncology. Further molecular testing demonstrated EGFR and ALK wild-type; 100% of tumour cells stained positive for programmed death-ligand 1 (PD-L1) by immunohistochemistry using the 22C3 clone (Dako Agilent, Santa Clara, CA, USA), rendering her suitable for consideration for first line pembrolizumab immune checkpoint inhibitor (ICPI) therapy.

She commenced pembrolizumab monotherapy and after three cycles of treatment her CT response assessment evaluation scan demonstrated a partial response (right upper lobe mass reduced by 60% and regression of lymphadenopathy). She continued on pembrolizumab but developed increasing dyspnoea after the fifth cycle. A CT scan identified pneumonitis (grade 2), for which she was commenced on prednisolone. Her pembrolizumab was paused and restarted after completing a steroid wean. She continues to receive pembrolizumab with an ongoing partial response 7 months after commencing treatment.

What is the evidence base for using ICPI therapy in the first line setting for patients with NSCLC?

What are the clinical characteristics of patients who respond to ICPIs?

What are the contraindications to ICPIs and for which treatment-related toxicities should the patient with lung cancer give consent?

How may the efficacy of ICPIs for patients with lung cancer be enhanced?

What is the evidence base for using ICPI therapy in the first line setting for patients with NSCLC?

Platinum-based doublet systemic chemotherapy is the standard of care for metastatic NSCLC.1 In recent years the identification of oncogenic drivers (EGFR, ALK, ROS) in patients with lung cancer has meant the development of new targeted agents, which has improved outcomes. In the majority of patients with non-oncogene-addicted NSCLC, however, there have been no major advances in systemic treatment until the advent of ICPI therapy.

The benefit of the ICPIs nivolumab and pembrolizumab in lung cancer was initially demonstrated in the relapsed (second line and beyond) setting and subsequently (as in this case) for use in the first line setting (Table 6.1)

Table 6.1Trials of ICPIs of patients with NSCLC in the first line setting.

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