Cisplatin plus Irinotecan or Etoposide for Neuroendocrine Cancers of the GI Tract?

Extrapulmonary high-grade neuroendocrine cancers (NEC) are treated like small-cell lung cancer, with case series indicating similar responses to systemic therapy. Clinical trials have not addressed optimal treatment for this aggressive disease.

Investigators from Japan now report results of the phase 3, randomized TOPIC-NEC trial comparing chemotherapy with etoposide plus cisplatin (EP) versus irinotecan plus cisplatin (IP) in patients with advanced high-grade NEC of the gastrointestinal tract. Of 170 patients, 69% were men, the most common primary sites were hepatobiliary (41%) and stomach (32%), 94% had metastatic or recurrent disease, 46% had large-cell cancers and 39% had small-cell cancers. Only 2.9% of patients had grade 3 neuroendocrine tumors.

The primary endpoint of overall survival was similar in the EP and IP groups (median, 12.5 and 10.9 months; hazard ratio, 1.04; P=0.80); rates of progression-free survival were also similar (5.6 and 5.1 months; HR, 1.06). These outcomes were similar in analyses of subgroups, including small- versus large-cell cancers, although a post hoc analysis indicated higher overall survival with EP compared with IP in the subgroup with poorly differentiated pancreatic NEC (median, 18.6 vs. 7.9 months).

The EP group had higher rates of grade 3/4 hematologic toxicity, including neutropenia (91.5% vs. 53.7%) and neutropenic fever (26.8% vs. 12.2%); the investigators amended the protocol to recommend prophylactic granulocyte colony-stimulating factor (G-CSF) for patients receiving EP. Grade 3/4 diarrhea was more common with IP than EP (47.6% vs. 23.2%).