Atezolizumab in Large Cell Neuroendocrine Carcinoma

Large-cell neuroendocrine carcinoma (LCNEC) of the lung is a rare and aggressive malignancy with limited prospective evidence to guide systemic treatment. This prospective, non-randomized, real-world study evaluated the effectiveness and safety of atezolizumab in combination with platinum-etoposide chemotherapy in treatment-naïve patients with metastatic lung-derived LCNEC. Patients who received atezolizumab were treated with carboplatin, etoposide, and atezolizumab, followed by atezolizumab maintenance in patients without disease progression for up to 24 months, or until disease progression, unacceptable toxicity, withdrawal of consent, or investigator decision, whichever occurred first. Patients in the control cohort received carboplatin and etoposide alone. The main clinical outcomes were progression-free survival, overall survival, overall response rate, and duration of response. Exploratory translational analyses included plasma microRNA assessment, including miR-375 and miR-21, in available blood samples.

Cohorts A and B: Inclusion Criteria: * Histologically confirmed Stage IV (metastatic) or unresectable locally advanced LCNEC * No prior treatment * With or without brain metastasis, if symptomatic patients should be treated with WBRT first * Performance Status ≤ 2 * Life expectancy \> 3 months * Written informed consent * Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 Exclusion Criteria: * Prior treatment with chemotherapy, immunotherapy, targeted small molecule therapy, or radiation therapy (except WBRT for brain metastasis from LCNEC) * Active or history of autoimmune disease or immune deficiency * Treatment with systemic immunosuppressive medications with the following exceptions: Patients who have received acute, low-dose systemic immunosuppressant medication (≤ 10 mg/day oral prednisone or equivalent) or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) are eligible for the study after Medical Monitor approval has been obtained. * Major surgical procedure other than for diagnosis within 4 weeks before initiation of study treatment, or anticipation of need for a major surgical procedure during the study * Active malignancy or malignancy within 3 years * Active tuberculosis * Current severe, uncontrolled systemic disease other than cancer * Known clinically significant liver disease * Treatment with any other investigational agent or participation in another clinical study with therapeutic intent