Multiple drugs

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An event is serious (based on the ICH definition) when the patient outcome is:

• * death

• * life-threatening

• * hospitalisation

• * disability

• * congenital anomaly

• * other medically important event

An 82-year-old woman developed pneumonitis during treatment with osimertinib for locally advanced lung adenocarcinoma. Additionally, she developed Pneumocystis jirovecii pneumonia (PJP) secondary to gefitinib, betamethasone, hydrocortisone and dexamethasone use [not all dosages stated; routes not stated].

The woman presented to a hospital in France with complaint of dyspnoea in October 2020. She had been diagnosed with locally advanced lung adenocarcinoma in June 2020. Osimertinib initiaited as a first-line treatment. However, after one month, she developed pneumonitis whose origin, after multidisciplinary consultation, was possibly attributed to osimertinib.

The woman started receiving betamethasone 6mg and then at rapidly tapered doses, resulting in good resolution of the pneumonitis. After six weeks, betamethasone dose reduced to 1mg, and then switched to hydrocortisone 20mg. Osimertinib was replaced by gefitinib after two weeks of betamethasone therapy. The therapy with betamethasone and low-dose hydrocortisone led to a good response. At the time of current presentation, her complaints started a couple of days before with delirium, dyspnoea and fever. Diffuse rhonchi were found on pulmonary auscultation. The results of the blood analysis were: leukocytes 8.1 × 10 ⁹ cells/L, neutrophils 7 × 10 ⁹ cells/L, lymphocytes 0.46 × 10 ⁹ cells/L, platelets 398 × 10 ⁹ cells/L, haemoglobin 10.1 g/dL, and C-reactive protein 341 mg/L. The chest CT scan revealed multiple bilateral apical and peri-hilar ground glass opacities associated with subpleural condensation. These findings were consistent with possible COVID-19 pneumonia. However, it was ruled out after RT-PCR test performed on nasopharyngeal swab on admission, two days after the symptoms began. Therefore, dexamethasone was recommended. When the initial course did not show favorable result, oxygen therapy was increased, and a second RT-PCR for COVID-19 was again negative. Therefore, a blood (1-3)-β-D-glucan test was performed, which showed a positive result at 90 pg/mL. PCR for Pneumocystis jirovecii was positive on bronchoalveolar lavage. A final diagnosis of PJP secondary to gefitinib use was made. She received treatment with Co-trimoxazole [sulfamethoxazole/trimethoprim] with a favorable outcome. The role of prolonged corticosteroids use such as betamethasone, hydrocortisone and dexamethasone could not be ruled out for the development of PJP.