Concurrent Nivolumab-Induced Gastritis and Cholangitis Accompanied by Biliary Tract Hemorrhage in a Patient With Stage IV Lung Adenocarcinoma.

Immune checkpoint inhibitors, including nivolumab, can result in immune-related adverse events (irAEs) that may affect multiple organ systems. Among irAEs, both gastritis and cholangitis are uncommon. We present the case of a 65-year-old man who received nivolumab for lung adenocarcinoma presented with epigastric pain. He was diagnosed with immune-related gastritis and cholangitis based on imaging and pathological findings. We administered prednisolone (1 mg/kg/day), which improved the patient's gastritis and relieved his pain. However, he experienced recurrent epigastric pain during corticosteroid tapering, and magnetic resonance imaging showed biliary tract hemorrhage. After watchful waiting, the hemorrhage improved without additional immunosuppressants. Immune-related gastritis, immune-related cholangitis, and their coexistence should be considered in patients who develop epigastric pain during immune checkpoint inhibitor therapy. When patients with concurrent immune-related gastritis and cholangitis complain of recurrent epigastric pain, it is important to assess which of these two irAEs is worsening because the optimal immunosuppressants differ between the two.

Lenvatinib-refractory thymic mucinous carcinoma with PIK3CA mutation.

Mucinous adenocarcinoma, a very rare type of thymic carcinoma, is aggressive and has a poor prognosis. The optimal treatment for advanced thymic mucinous adenocarcinoma has not yet been established because of its rarity. An oral multi-tyrosine kinase inhibitor, lenvatinib, was approved for treatment of thymic carcinoma in March 2021 in Japan. However, to the best of our knowledge, there are no published reports concerning lenvatinib for thymic mucinous adenocarcinoma. Herein, we report a 39-year-old woman who presented with a 70 mm multilocular cystic tumor in her left anterior mediastinum and a massive pericardial effusion. We diagnosed a Masaoka stage IVb thymic mucinous adenocarcinoma with multiple metastases to the liver and bones, and pericardial dissemination on the basis of the pathologic findings on examination of a video-assisted thoracoscopic tumor biopsy and radiological examinations. She received paclitaxel-carboplatin-based chemotherapy, but developed a left cerebellar metastasis. Second-line chemotherapy with lenvatinib failed to suppress the tumor. She died of cancer progression 5 months after presentation. Here, we report what we believe to be the first case of a thymic mucinous adenocarcinoma treated with lenvatinib. Our patient's thymic mucinous adenocarcinoma was refractory to both cytotoxic chemotherapy and lenvatinib. Using next-generation sequencing, we identified phosphatidylinositol 3-kinase catalytic subunit alpha mutation in the tumor. We suspected an association between this mutation and resistance to lenvatinib. We therefore recommend performing next-generation sequencing when considering introduction of lenvatinib for thymic mucinous adenocarcinoma. A surgical procedure may be necessary for accurate diagnosis and genetic analysis of this histological tumor type.

Successful Dasatinib Treatment of Epidermal Growth Factor Receptor-Mutant Lung Adenocarcinoma and BCR-ABL1-Positive Chronic Myeloid Leukemia: A Case Report.

Dasatinib, a second-generation BCR-ABL1 tyrosine kinase inhibitor (TKI), inhibits multiple kinase pathways and is a promising anti-tumor agent for various solid tumors, including lung cancer. Herein, we report a patient with coexisting epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma and BCR-ABL1-positive chronic myeloid leukemia (CML). The patient received afatinib for a postoperative intrapulmonary recurrence of lung adenocarcinoma harboring EGFR exon 19 deletion. Tumor reduction was achieved with afatinib; however, dose reduction was required because of grade 2 diarrhea and skin toxicity. The reduced dose maintained a partial response. Thirty-one months after introduction of afatinib, he was diagnosed as having BCR-ABL1-positive CML and nilotinib was added to his treatment regimen. However, the combination of nilotinib and afatinib aggravated his diarrhea, prompting discontinuation of afatinib. Because nilotinib does not have sufficient anti-tumor efficacy for CML, dasatinib was substituted for nilotinib. Thirty-five months after introduction of dasatinib, bosutinib was substituted for dasatinib because of uncontrollable pleural effusions. Dasatinib achieved 31- and 35-month progression-free survivals for CML and EGFR-mutant lung adenocarcinoma, respectively. Dasatinib is thus a therapeutic option for coexisting EGFR-mutant lung adenocarcinoma and BCR-ABL1-positive CML when TKI combination therapy is contraindicated by severe adverse events. In our patient, adding nilotinib to afatinib led to severe diarrhea. When administering TKI combination therapy, drug-drug interactions should be considered.