Chromosomal rearrangements involving the c-ros oncogene 1 (ROS1) are identified in approximately 1% of non-small cell lung cancer (NSCLC) patients. Crizotinib is the first tyrosine kinase inhibitor (TKI) against ROS1-rearranged NSCLC. G2032R, a secondary resistant mutation, is observed in 41% of patients treated with crizotinib. Entrectinib, a TKI against neurotrophic tropomyosin receptor kinase, is reportedly efficacious against ROS1-rearranged NSCLC. However, ROS1-G2032R is resistant to entrectinib both in vitro and in vivo. We report an 85-year-old female patient with ROS1-rearranged NSCLC, who developed drug-induced interstitial lung disease (DI-ILD) 2 months after crizotinib treatment, and was treated with prednisolone followed by entrectinib. Entrectinib treatment resulted in stable disease with a marginal response after a partial response to crizotinib. Entrectinib treatment following crizotinib cessation due to DI-ILD was efficacious, which suggested that ROS1-G2032R gatekeeper mutation, frequently observed in crizotinib-resistant disease, was absent.K E Y W O R D S crizotinib, c-ros oncogene 1, drug-induced interstitial lung disease, entrectinib, non-small cell lung cancer
Large‐cell neuroendocrine carcinomas (LCNECs), categorized as high‐grade neuroendocrine carcinomas, account for approximately 3% of resected lung cancers. LCNECs containing other components are called ‘combined LCNECs’ and have no standard treatment. A 73‐year‐old male with a metastatic brain tumour from a combined LCNEC of the lung containing adenocarcinoma and sarcomatoid components was referred to our department. The patient was treated with chemotherapy consisting of carboplatin and nanoparticle albumin‐bound (nab)‐paclitaxel in combination with atezolizumab, which was decided in accordance with the histological evaluation of the components. This treatment resulted in partial response and remained durable for 12 months with an ongoing regimen. The current case suggests that the constituents of chemoimmunotherapy should be selected in accordance with the reported efficacy of relevant regimens for each component of the combined LCNEC.
Pulmonary pleomorphic carcinoma (PPC) is well-known for its aggressive nature that is usually resistant to platinum-based chemotherapy. On the other hand, the efficacy of an immune checkpoint inhibitor-based regimen in PPC has been elucidated. PPCs harboring epidermal growth factor receptor (EGFR) mutations are extremely rare, and the efficacy of EGFR-tyrosine kinase inhibitors in PPC is limited compared to their efficacy in EGFR-mutated adenocarcinoma. A 43-year-old female patient presenting with a lung mass with multiple brain metastases, carcinomatous pericarditis, and multiple bone metastases was referred to our department. Transbronchial biopsy confirmed the diagnosis of PPC harboring an EGFR mutation with exon 19 deletion. Subsequently, she was treated with osimertinib, a third-generation EGFR-tyrosine kinase inhibitor, which resulted in partial response with shrinkage of the primary lesion and brain metastases. This partial response remained durable for 11 months with an ongoing regimen. The current case suggests that osimertinib would show promising effects as a first-line treatment for PPCs harboring EGFR mutations, as well as a reasonable sequence of therapy followed by immune checkpoint inhibitor-based regimens.
An esophageal stricture is an abnormal esophageal narrowing, usually caused by esophageal diseases and rarely by lung cancer. They cause malnutrition, performance status (PS) deterioration, and difficulty in the oral administration of antitumor drug tablets. A 78-year-old female patient with lung adenocarcinoma, harboring an epidermal growth factor receptor (EGFR)-sensitizing mutation, experienced dysphagia due to an esophageal stricture caused by retrotracheal lymph node metastases. Osimertinib is a third-generation EGFR-tyrosine kinase inhibitor that is efficacious against EGFR-sensitizing mutations.The esophageal stricture hampered food intake and oral administration of osimertinib, causing severe malnutrition and deterioration to PS 3. Esophagogastroduodenoscopy (EGD) revealed severe and entire circumferential stenosis (7 cm in length) of the upper esophagus without mucosal abnormality. A nasogastric tube was inserted under EGD guidance, and an osimertinib suspension was administered accordingly: a tablet containing 80 mg of osimertinib was suspended in 50 mL of sterile hot water (55 ℃) for ten minutes, and the suspension was administered through a nasogastric tube once daily. Dysphagia improved 15 days after the introduction of osimertinib. After 21 days, the patient could take foods and drugs orally, and her PS improved to 1. Administering an osimertinib suspension via a nasogastric tube was a viable option in managing esophageal strictures in patients with EGFR-sensitizing mutations.
The incidence rate of pseudoprogression during immune checkpoint inhibitor monotherapy for non-small cell lung cancer is reportedly 3.6%-6.9%, while pseudoprogression during chemoimmunotherapy is rare. Reports on pseudoprogression during dual immunotherapy combined with chemotherapy are lacking. Herein, a 55-year-old male with invasive mucinous adenocarcinoma (cT2aN2M1c [OTH, PUL], stage IVB, and programmed death-ligand 1 expression <1%), renal dysfunction, and disseminated intravascular coagulation was treated with carboplatin, solvent-based paclitaxel, nivolumab, and ipilimumab. After treatment initiation, computed tomography (CT) on day 14 showed disease progression. The patient was diagnosed with pseudoprogression because of a lack of symptoms, improved platelet count, and decreased fibrin/fibrinogen degradation product levels. CT on day 36 showed a reduction in the primary lesion size, multiple lung metastases, and mesenteric metastases. Therefore, pseudoprogression should be considered during dual immunotherapy with chemotherapy.
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