Mefatinib as first-line treatment of patients with advanced EGFR-mutant non-small-cell lung cancer: a phase Ib/II efficacy and biomarker study.

EGFR inhibitors have revolutionized the treatment of advanced non-small-cell lung cancer (NSCLC). Mefatinib is a novel, bioavailable, second-generation, irreversible pan-EGFR inhibitor. This phase Ib/II open-label, single-arm, multi-center study investigated the efficacy, safety, biomarker, and resistance mechanisms of mefatinib in the first-line treatment of patients with advanced EGFR-mutant NSCLC. This study included 106 patients with EGFR-mutant stage IIIB-IV NSCLC who received first-line mefatinib at a daily dose of either 60 mg (n = 51) or 80 mg (n = 55). The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. The cohort achieved an ORR of 84.9% and DCR of 97.2%. The median PFS was 15.4 months and the median OS was 31.6 months. Brain metastasis was detected in 29% of patients (n = 31) at diagnosis and demonstrated an ORR of 87.1%, PFS of 12.8 months, and OS of 25.2 months. Adverse events primarily involved skin and gastrointestinal toxicities, which were well-tolerated and manageable. Analyses of mutation profiles were performed using targeted sequencing of plasma samples at baseline, first follow-up 6 weeks from starting mefatinib therapy (F1), and at progression. Patients with concurrent TP53 mutations had comparable PFS as wild-type TP53 (14.0 vs 15.4 months; p = 0.315). Furthermore, circulating tumor DNA clearance was associated with longer PFS (p = 0.040) and OS (p = 0.002). EGFR T790M was the predominant molecular mechanism of mefatinib resistance (42.1%, 16/38). First-line mefatinib provides durable PFS and an acceptable toxicity profile in patients with advanced EGFR-mutant NSCLC.

A Talaromyces marneffei infection with osteolytic lesions in an HIV-negative patient at non-endemic areas: A case report.

Talaromyces marneffei infection is an endemic opportunistic infection for immunodepression patients, especially HIV-positive patients. Our case describes an unendemic and HIV-negative patient who presented with fever, subcutaneous mass, osteolytic destruction of the skull and subcutaneous abscess penetrating the diseased skull. The growth of Talaromyces marneffei was identified by the culture of the frontal pus, sputum, blood and bone marrow. Due to severe nausea and vomiting during the use of amphotericin B, voriconazole was finally selected for treatment. Two weeks after intravenous infusion of voriconazole injection, the patient was given oral voriconazole tablets for 5 months. After the initial intravenous treatment of voriconazole, the patient developed increased dyspnea and required ventilator support with endotracheal intubation, and methylprednisolone was given intravenously for 5 days. All lesions absorbed and no obvious discomfort was found during the follow-up at the third month after discharge. At present, the patient has been followed up for more than 3 years without recurrence. The case aims to raise doctors' awareness of this rare disease in non-endemic areas and HIV-negative patients.

Two cases of pulmonary cysticercosis manifesting as pleural effusion: case report and literature review.

Cysticercosis is an important public health problem in developing countries. The major involvement sites are the central nervous system and the eyes, although striated muscles and subcutaneous tissues are frequently involved in the disseminated form of disease. Pulmonary involvement in cysticercosis is very rare and ill-defined nodular shadows distributed throughout the lung is the usual radiological presentation. Only one case of cysticercosis presenting as lung cavity with pleural effusion has been reported so far in literature. We describe two cases in which pleural effusion due to cysticercosis were detected on chest X-ray and computed tomography (CT) scan.

Acute Disseminated Talaromyces marneffei in An Immunocompetent Patient.

Talaromyces marneffei (also called Penicilliosis Marneffei or T. marneffei) is a rare fungal disease that is prevalent mainly in Southeast Asia and commonly seen in immunocompromised hosts. It was rarely observed in immunocompetent hosts. We report a case of acute disseminated T. marneffei in an immunocompetent patient in the non-prevalent region. This patient had never visited the endemic area. The patient experienced a persistent fever. Brain CT and magnetic resonance imaging (MRI) showed a mass in the right frontal with osteolytic damage. Excessive white blood cell (WBC) count and C-reactive protein content were observed. Antibiotics including meropenem and linezolid could not play an effect, and another two hard masses appeared in his right neck and front chest wall. The aspirates from the right frontal mass and bone marrow were cultured. The final diagnose of this infection was disseminated T. marneffei. After voriconazole treatment, all symptoms improved gradually. We present this case and aim to promote more clinicians and microbiologists in the non-endemic region to recognize this rare disease.