Head-to-head: Etoposide and irinotecan equally effective in neuroendocrine carcinoma

Etoposide and irinotecan showed equal efficacy in a head-to-head study among patients with advanced neuroendocrine carcinoma (NEC) of the digestive system [1]. Therefore, these agents both remain first-line therapeutic options for this population.

“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 [1]



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.”

1. 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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Posted on 21 March, 20224 April, 2024