Etoposide plus cisplatin (EP) and irinotecan plus cisplatin (IP) appear similarly effective in patients with platinum-naive, advanced digestive neuroendocrine carcinoma (NEC), results of the phase 3 TOPIC-NEC trial suggest.

“Results of this randomized clinical trial demonstrate that both EP and IP remain the standard first-line chemotherapy options,” researchers wrote in JAMA Oncology.

The TOPIC-NEC trial enrolled 170 patients at 50 centers in Japan. The patients had chemotherapy-naive, recurrent or unresectable digestive NEC and were randomly assigned to receive EP (n=84) or IP (n=86). 

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The median age was 64 (range, 38-75) years in the EP arm and 65 (range, 29-75) years in the IP arm. Roughly 69% of patients in each arm were men. The primary site was the gastrointestinal tract for 59.5% of patients in the EP arm and 58.1% of those in the IP arm. Most patients (73.8% and 72.1%, respectively) had metastatic disease.

Patients treated with EP received etoposide at 100 mg/m2 on days 1, 2, and 3 and cisplatin at 80 mg/m2 on day 1 every 3 weeks. Patients treated with IP received irinotecan at 60 mg/m2 on days 1, 8, and 15 and cisplatin at 60 mg/m2 on day 1 every 4 weeks. They were treated until progression, intolerability, or consent withdrawal.

There was no significant difference in overall survival (OS) between the 2 arms. The median OS was 12.5 months with EP and 10.9 months with IP (hazard ratio [HR], 1.04; 90% CI, 0.79-1.37; P =.80). The 1-year OS rate was 52.1% and 41.8%, respectively. 

“Although the primary analyses revealed no statistically significant difference in OS between the 2 arms, the study was not designed to assess the equivalence of the 2 regimens,” the researchers noted. “Therefore, the 2 regimens should not be recognized as equivalent, but rather as they do not differ beyond a certain level.”

As with OS, there was no significant difference in progression-free survival (PFS) or objective response rate (ORR) between the arms. The median PFS was 5.6 months with EP and 5.1 months with IP (HR, 1.06; 95% CI, 0.78-1.45). The ORR was 54.5% and 52.5%, respectively (P =.87). 

Grade 3-4 adverse events were more common in the EP arm than in the IP arm. Common grade 3-4 events (in the EP and IP arms, respectively) included neutropenia (91.5% vs 53.7%), leukopenia (61.0% vs 30.5%), and febrile neutropenia (26.8% vs 12.2%). 

The initially high rate of febrile neutropenia in the EP arm was reduced with primary prophylactic use of granulocyte colony-stimulating factor, the researchers noted. 

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Morizane C, Machida N, Honma Y, et al. Effectiveness of etoposide and cisplatin vs irinotecan and cisplatin therapy for patients with advanced neuroendocrine carcinoma of the digestive system. The TOPIC-NEC phase 3 randomized clinical trial. JAMA Oncol. Published online August 18, 2022. doi:10.1001/jamaoncol.2022.3395

This article originally appeared on Cancer Therapy Advisor