“Platinum-based chemotherapy regimens are recommended for advanced NEC,” said Dr Chigusa Morizane (National Cancer Center Hospital, Japan). “Etoposide plus cisplatin (EP) and irinotecan plus cisplatin (IP) are standard-of-care options for patients with this condition. However, it is currently unknown which combination is more effective.” Therefore, the phase 3 TOPIC-NEC study (UMIN000014795) was designed to compare EP and IP head-to-head in patients with advanced NEC (n=170). The patients were randomised 1:1 to either EP: etoposide (100 mg/mg2, day 1, 2, 3) and cisplatin (80 mg/m2, day 1, every 3 weeks); or IP: irinotecan (60 mg/m2, day 1, 8, 15) and cisplatin (60 mg/m2, day 1, every 4 weeks).
The median overall survival (OS), primary endpoint of this study, did not differ significantly between EP and IP (12.5 vs 10.9 months; P=0.80). Similarly, the median progression-free survival (PFS) times were comparable (5.6 vs 5.1 months, respectively; P=0.72). The objective response rates were also similar for patients in the EP and IP arm (54.5% vs 52.5%, repectively). Interestingly, a post-hoc subgroup analysis showed that patients with pancreatic poorly differentiated NEC may benefit more from EP therapy (HR 4.10; 95% CI 1.26–13.31).
The safety analysis showed that grade 3 or 4 reductions in neutrophil count were more common in the EP group than in the IP group (91.5% vs 53.7%). Also, grade 3 or 4 febrile neutropenia occurred more often in the EP arm (26.8% vs 12.2%; see Figure). Notably, prophylactic administration of granulocyte colony-stimulating factor (G-CSF) reduced the prevalence of grade 3 or 4 neutropenia from 27.9% to 9.5% in the first treatment cycle. Finally, patients in the IP arm experienced more any-grade diarrhoea than those in the EP arm (47.6% vs 23.2%).
Figure: Safety profiles of etoposide plus cisplatin versus irinotecan plus cisplatin 
Dr Morizane concluded that both regimens remain first-line standard-of-care options for patients with NEC of the digestive system. “Future studies should investigate whether additional immune checkpoint inhibitors may provide benefits for our patients.”
- Morizane C, et al. Randomized phase 3 study of etoposide plus cisplatin versus irinotecan plus cisplatin in advanced neuroendocrine carcinoma of the digestive system: A Japan Clinical Oncology Group study (JCOG1213, TOPIC-NEC). Abstract 501, ASCO GI 2022, 20–22 January.
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