Immunotherapy Combination Demonstrates Efficacy in Patients With Rare Neuroendocrine Tumors

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Data from a phase 2 study demonstrated that high-grade neuroendocrine carcinoma had a 42% overall response rate to the combination of nivolumab and ipilimumab.

An immune checkpoint inhibitor combination is showing efficacy in patients with high-grade neuroendocrine carcinoma, offering a glimmer of hope for patients with the rare cancer, and the doctors who treat them.

According to data from a phase 2 study presented at the American Association for Cancer Research’s Annual Meeting 2019, being held in Atlanta, Georgia, March 29 to April 3, the combination of nivolumab (Opdivo) and ipilimumab (Yervoy), which has already demonstrated efficacy in more common cancers like non—small cell lung cancer, has demonstrated a 42% response rate among patients with high-grade neuroendocrine carcinoma.

“Given that the current options for patients with high-grade neuroendocrine carcinoma are generally limited to aggressive chemotherapy regimens, this is an exciting find for this population,” Sandip Patel, MD, associate professor of medicine at the University of California San Diego School of Medicine, medical oncologist at Moores Cancer Center at US San Diego Health, and author of the study, said in a statement.

The Dual Anti-Cytotoxic T Lymphocyte Antigen-4 and Programmed Cell Death 1 Blockade in Rare Tumors (DART) trial tested the combination in patients with rare cancers, 33 of which had neuroendocrine tumors. Among these 33 patients, 58% had high-grade disease, and the most common sites of disease were gastrointestinal (45%) and lung (18%).


During the study period, the overall response rate for patients with neuroendocrine tumors was 24%, which included 1 complete response and 7 partial responses. Notably, these responses were concentrated among patients with high-grade disease.

“We only observed complete and partial responses among patients with high-grade carcinoma, and one preliminary hypothesis for this finding is that high-grade neuroendocrine carcinomas may have a higher tumor mutational burden, which is an indicator of better response to immunotherapy,” noted Patel.

According to Patel, the researchers are planning on verifying these results later this year, specifically in patients with high-grade neuroendocrine carcinoma, as a separate cohort of the DART trial.

Looking at the secondary endpoints, the 6-month progression-free survival was 30% and median overall survival was 11 months.

The combination was also well-tolerated among patients, with the most common toxicities including fatigue (30%) and nausea (27%). Alanine aminotransferase elevation (9%)—indicative of abnormal liver function—was the most common immune-related adverse event. There were no observed grade 5 immune-related adverse events.

Patients with pancreatic neuroendocrine tumors are currently being assessed in a separate ongoing cohort of the DART study.


Patel S, Othus M, Chae Y, et al. A phase II basket trial of dual anti—CTLA-4 and anti–PD-1 blockade in rare tumors (DART) S1609: the neuroendocrine cohort. Presented at: the American Association for Cancer Research’s Annual Meeting; March 31, 2019; Atlanta, Georgia. Abstract CT039.