Multiple drugs

Abstract

Hyperprogression of pulmonary pleomorphic carcinoma: case report A 66-year-old man had hyperprogression of pulmonary pleomorphic carcinoma (hyperprogressive of disease) during treatment with atezolizumab for pulmonary pleomorphic carcinoma. The man also exhibited lack of efficacy during treatment with afatinib and osimertinib for pulmonary pleomorphic carcinoma [routes and dosages not stated]. The man, who had been diagnosed with pulmonary pleomorphic carcinoma of the right lower lobe with metastasis to the brain, lungs, pleura and mediastinal lymph nodes, received afatinib and osimertinib. However, he did not respond to afatinib and osimertinib. Hence, he received four cycles of carboplatin and pemetrexed chemotherapy, with partial response. Then, he had undergone talc pleurodesis for right sided malignant pleural effusion. Subsequently, he received whole-brain radiation for multiple brain metastases. Thereafter, he was admitted to the hospital (current presentation). He subsequently started receiving atezolizumab as fourth line treatment. Upon admission, a chest radiography and computed tomography was performed which showed no pleural effusion and cardiac enlargement. Subsequent UCG showed small amount of pericardial fluid. After 3 days, he exhibited tachycardia, hypotension along with dyspnoea, requiring oxygen support. Subsequent X-ray and echocardiography showed mild cardiac enlargement and a marked accumulation of pericardial effusion, respectively. Based on symptoms and clinical investigations, he was diagnosed with cardiac tamponade. Hence, pericardial drainage was immediately performed. Following pericardial drainage, a chest radiography was performed which showed cardiac enlargement. A repeate chest CT scan showed significant worsening of multiple lung metastases, increased sizes of old lesions, bilateral ground-glass opacity, left pleural effusion and newly developed metastasis in the lung. His respiratory condition rapidly deteriorated and LDH level increased to 706 U/L. At the same time, the drug-induced pneumonia related to immune-related adverse events (irAE) was suspected. The man subsequently started receiving treatment with methylprednisolone. However, after 13 days from initiation of atezolizumab, he died due to respiratory failure. Based on symptoms and clinical investigation, he was diagnosed with atezolizumab-induced hyperprogressive of disease (HPD). Autopsy was performed which showed metastasis in all lobes of the bilateral lungs, new metastases in the liver and diaphragm, bilateral pleural effusion, pericardial fluid, cardiac tamponade due to carcinomatous pericarditis, carcinomatous lymphangiopathy and exacerbation of multiple lung metastases. Due to lack of strong evidence for irAE, drug-induced pneumonia was ruled out.