Platinum-doublet chemotherapy for advanced gastroenteropancreatic neuroendocrine carcinoma: A systematic review and meta-analysis.

Abstract

e16217 Background: Neuroendocrine carcinoma (NEC) is a poorly differentiated pathological neuroendocrine neoplasm exhibiting aggressive clinical behaviors; the most common extrapulmonary site is the gastroenteropancreatic (GEP) system. Treatment strategies for GEP-NEC are primarily based on those employed for small cell lung cancer, and platinum-doublet chemotherapy, such as platinum plus etoposide (EP) or platinum plus irinotecan (IP), has been widely used as initial systemic therapy for patients with advanced/metastatic disease; however, clinical data for GEP-NEC are chiefly derived from small-scale retrospective studies, and the reported efficacy is heterogenous among studies. Methods: We conducted a systematic database search using PubMed/MEDLINE and EMBASE. Eligible studies included randomized trials, single-arm trials, prospective observational studies, and retrospective studies documenting the clinical efficacy of platinum-doublet chemotherapy (EP and IP) for advanced GEP-NEC. The pooled overall response rate (ORR), median progression-free survival (PFS), and median overall survival (OS) were calculated and weighted using generic inverse variance in a random-effects meta-analysis model. Results: Based on initial screening and eligibility assessment, 19 studies with a combined total of 1,157 patients were identified through a systematic review. Studies included 3 comparative studies between EP and IP with 1 randomized phase II trial and 2 retrospective studies. The pooled ORR in all patients who received the platinum-doublet regimen was 49.1% (95% confidence interval [CI], 41.8–56.5), and subgroup analysis for EP and IP groups showed ORRs of 44.4% (95% CI, 35.9–53.0) and 59.4% (95% CI, 48.0–70.8), respectively. According to the three studies directly comparing EP to IP, the odds ratio of ORR using EP as reference was 1.95 (95% CI, 0.86–4.39, P = 0.11). The pooled median OS in all patients who received the platinum-doublet regimen was 12.9 (95% CI, 10.9–15.3) months, where EP and IP subgroups had median OS of 12.9 (95% CI, 10.8–15.4) and 12.9 (95% CI, 6.0–27.8) months, respectively. The pooled median PFS was 5.4 (95% CI, 4.5–6.4) months in all patients with platinum-regimen, 5.4 (95% CI, 4.5–6.5) months in the EP subgroup, and 4.0 (95% CI, 1.4–11.7) months in IP subgroup, respectively. Conclusions: This study was the first systematic review and meta-analysis assessing patients with GEP-NEC; it has revealed considerable ORR following platinum-doublet chemotherapy. EP and IP regimens can be reasonably employed in patients with advanced GEP-NEC. These results can serve as reference information for clinicians in deciding a suitable chemotherapy regimen. Larger randomized trials and individual patient data meta-analyses are warranted to obtain robust clinical evidence.