A population based analysis of outcome of chemotherapy for metastatic pulmonary large cell neuroendocrine carcinomas: does the regimen matter?

It is unclear what constitutes optimal chemotherapy for metastatic pulmonary large cell neuroendocrine carcinoma (LCNEC). Expert opinion based guidelines favor platinum-etoposide, i.e. small cell lung carcinoma (SCLC) type chemotherapy treatment. However, data are lacking due to low incidence of LCNEC and changes in diagnosis after pathology revision. In a population based, pathology revised LCNEC series we compared overall survival (OS) of non-small cell lung carcinoma (NSCLC) and SCLC type chemotherapy treatment. Data of the Dutch Pathology Registry (PALGA) and Netherlands Cancer Registry were combined and searched for patients with stage IV definite LCNEC and possible LCNEC treated with chemotherapy, diagnosed between 2003-2012. In 207 patients original tumor specimen slides were available for central revision blinded for clinical information. Data on clinical characteristics, chemotherapy and OS were retrieved. First-line platinum chemotherapy was clustered: 1) NSCLC type treatment including gemcitabine, docetaxel, paclitaxel and vinorelbine, 2) pemetrexed (Pem-NSCLC), and 3) SCLC type treatment including etoposide. Multivariate regression analysis included variables significant at univariate analysis and the variables gender and age. 128 patients had panel-consensus definite LCNEC. 62% (N = 79) received ≥4 cycles and 26% (N = 33) ≤2 cycles of chemotherapy. NSCLC type chemotherapy was administered in 46% (N = 60), Pem-NSCLC in 16% (N = 20), and SCLC type in 38% (N = 48) patients. NSCLC type chemotherapy treated patients had a median OS of 8.5 [95% confidence interval (CI) 7.0-9.9] months, significantly higher than treatment with Pem-NSCLC; median 5.9 [95% CI 5.0-6.9] months (Hazard Ratio (HR) = 2.51 [95% CI 1.39-4.52], p = 0.002) and SCLC; median 6.7 [95% CI 5.0-8.5] months (HR = 1.66 [1.08-2.56], p = 0.02). This population based analysis on outcome of chemotherapy in patients with panel-consensus LCNEC shows that NSCLC type chemotherapy treatment leads to prolonged OS when compared to SCLC and Pem-NSCLC type chemotherapy treatment.