Carboplatin-etoposide chemotherapy for patients with advanced extra-pulmonary (EP) poorly differentiated (PD) neuroendocrine carcinoma (NEC); outcomes from a European Neuroendocrine Tumour Society Centre of Excellence

Introduction: Platinum-etoposide is considered standard-of-care first-line treatment for patients diagnosed with advanced EP-PD-NECs. The optimal platinum-etoposide schedule remains undefined; carboplatin is often substituted for cisplatin, although quality data is lacking. Methods: Electronic records of patients with advanced EP-PD-NEC treated with carboplatin-etoposide (06/09-02/17) were reviewed retrospectively, with aim to provide real-life efficacy/safety data on carboplatin-etoposide in this setting. Chi-square test, Kaplan-Meier and univariate/multivariable Cox-regression analyses were performed, as appropriate. Results: Seventy-three patients were screened, 57 eligible; median follow-up 8.57 months (m); median age 70.4 years (range 36.2–88.4). Most patients were male (68.4%), had Eastern-Cooperative-Oncology-Group performance-status (ECOG-PS) 0–1 (79%) and none-mild comorbidities (72%). Site of primary tumour: foregut 35.1%, hindgut 24.6%, unknown 21%, pancreas 8.8%, others 10.5%. Most had stage IV disease (87.7%); median number of metastatic sites: 2 (range 1–6), liver (68%) being the most common. Histopathology: median Ki-67 75% (95%-Confidence-Interval (95%-CI) 60–80%); morphology included small-cell (33.3%), large-cell (22.8%), others (3.5%), not-specified (40.4%). The 57 patients received a total of 64 courses of carboplatin-etoposide: 54 (84.4%) first-line, 9 (14%) second-line and 1 (1.6%) third-line. Etoposide was administered orally (81.2%) or intravenously (18.8%); median number of cycles: 4 (range 1–7). In the first- and second-line settings, median progression-free-survival (PFS) was 5.4 m (95%-CI 3.6–6.9) and 3.4 m (95%-CI 1.6–11.0) and median overall-survival was 7.5 m (95%-CI 6.2–11.5) and 5.8 m (95%-CI 1.6–15.4), respectively. Most common grade 3–4 adverse events in first/second-line were myelotoxicity (29.6%/44.4%), infections (13%/11.1%), venous thromboembolism (11.1%/22.2%); no differences between first-/second-line were identified (all P-values >0.05). Median carboplatin-etoposide dose-intensity was 94.8 and 94.4% in first-/second-line, respectively. Line of chemotherapy did not impact PFS (P-value >0.3). Liver metastases and age were significant in the univariate analysis for PFS and included in the multivariable Cox-regression: presence of liver metastases was the only independent factor related to worse PFS (Hazard-Ratio 1.9 (95%-CI 1.1–3.3); P-value 0.03). Conclusion: Carboplatin-etoposide is associated with survival outcomes in real-life comparable to those reported in current literature. It is an active combination for patients with advanced EP-PD-NECs, with a manageable toxicity profile which allows adequate dose-intensity.