Ramucirumab-containing chemotherapy for patients with gastrointestinal neuroendocrine carcinoma refractory/intolerant to platinum-based chemotherapy: A multicenter observational retrospective study (WJOG13420G).

No standard second-line chemotherapy has been established for gastrointestinal neuroendocrine carcinoma (NEC). This study aimed to determine whether ramucirumab (RAM) is a treatment candidate in this setting. We retrospectively collected data from patients with gastric and colorectal NEC who received second-line chemotherapy following platinum-based chemotherapy. The pathological diagnosis of NEC was confirmed centrally according to the World Health Organization 2019 classification. We compared the clinical outcomes between second- or later-line chemotherapy in the RAM group and second-line chemotherapy in the non-RAM group. One-hundred patients diagnosed with NEC by central pathological review were studied. The RAM and non-RAM groups included 44 (gastric/colorectal cancer, 34/10) and 56 (37/19) patients, respectively. In the RAM group, 68% of patients received RAM as second-line chemotherapy. RAM was most frequently combined with weekly paclitaxel for gastric NEC and FOLFIRI for colorectal NEC. The RAM group showed better trends in overall survival and progression-free survival than the non-RAM group, with a median of 9.0 versus 5.6 months and 4.3 versus 1.8 months, respectively (hazard ratios [HR]: 0.75 [95% CI: 0.45-1.28] and 0.45 [0.27-0.75]). Efficacy was more pronounced in gastric NEC (PFS HR: 0.32, OS HR: 0.56) compared to colorectal NEC (PFS HR: 0.82, OS HR: 1.47). The objective response rate was significantly higher in the RAM group (44%) than in the non-RAM group (6%), with notably higher responses observed in patients receiving paclitaxel plus RAM (62%). This study suggested that RAM-containing chemotherapy, especially paclitaxel plus RAM for gastric NEC, seems promising and should be further investigated.