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Case history

image A 71-year-old retired headmistress presented to her GP with a 2 month history of a non-productive cough and weight loss of 6 kg. A chest x-ray requested by her GP showed a mass in the right lower zone of her lungs and a small right-sided pleural effusion. She was referred urgently to her local hospital's respiratory clinic with suspected malignancy. Her medical history included hypertension, hypothyroidism and rheumatoid arthritis, for which she took lisinopril, levothyroxine and ibuprofen/co-codamol, respectively. She had no known drug allergies. She took regular, moderate exercise and her performance status (PS) was 1; she had never smoked and she drank alcohol occasionally and in moderation. She lived with her husband, had no children and no clinically relevant family medical history.

Investigations at the respiratory clinic confirmed a diagnosis of stage IV non-small-cell lung carcinoma (NSCLC). She was therefore referred to the oncology department after discussion among the multidisciplinary team (MDT).

  • CT chest/upper abdomen:

    • – right lower lobe 4.6 cm × 3.5 cm mass (long axis);

    • – right mediastinal lymph node 2.0 cm (short axis station 4R, lower paratracheal right-sided upper mediastinal node);

    • – small right-sided effusion;

    • – stage IV metastatic lung cancer: T2N2M1a.

  • Endobrachial ultrasound and cytology of right lower lobe lesion:

    • – adenocarcinoma;

    • – cytokeratin 7 (CK-7)-positive, thyroid transcription factor 1 (TTF-1)-positive;

    • ALK, KRAS, NRAS and EGFR mutation status awaited.

When seen the following week in the oncology clinic, she was very breathless, fatigued and her PS had declined to 3. On examination there was reduced air entry from the right mid-zone of her lung on auscultation and stony dullness to percussion to the top of the right mid-zone. Chest x-ray revealed a large right pleural effusion. She was admitted to hospital directly from the clinic and a right-sided chest drain was inserted under radiological guidance. Over the following 48 h, 1.2 l of serous fluid was drained, bringing considerable symptomatic improvement.

Molecular profiling confirmed the presence of a sensitizing EGFR mutation.

  • Genetic analysis:

    • EGFR exon 21 (L858R) point mutation;

    • KRAS wild-type;

    • NRAS wild-type;

    • ALK rearrangement-negative.

What are the aims of treatment in this case?

What are the treatment options for this patient?

What is the evidence behind the treatment plan?

What are the adverse effects of treatment and how are they managed?

What drives acquired disease resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs)?

What would you do next?

What future treatment options are there for this lady?

What are the aims of treatment in this case?

This woman has presented with metastatic NSCLC; therefore, the aims of treatment are symptom control, maintenance and maximization of quality of life (QOL), and lengthening of life expectancy. Given the palliative intent of management in this case, prescription of any anticancer treatments was taken with due regard for potential associated toxicities.

What are the treatment options for this ...

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