A combination of two common immunotherapy drugs shrinks rare, aggressive neuroendocrine tumors, according to new research results presented at the American Association for Cancer Research Annual Meeting 2019, held March 29-April 3 in Atlanta. Results from the SWOG Cancer Research Network trial known as DART, short for Dual Anti-CTLA-4 and Anti-PD-1 Blockade in Rare Tumors, show a significant clinical benefit for patients with high-grade neuroendocrine carcinoma, a cancer of the neuroendocrine cells that often forms tumors in the lungs and along the digestive tract.

Neuroendocrine carcinoma

This cancer is rare  about 12,000 people in the U.S. are diagnosed each year  but the general prevalence of the disease grew six-fold between 1973 and 2012. Patients with the high-grade, or rapidly growing, form have few treatment options. “We saw a benefit in patients with high-grade carcinoma; which is the population that really needs an effective treatment option;” said Sandip Patel, MD, the DART clinical study chair; an associate professor of medicine at the University of California at San Diego School of Medicine; and a medical oncologist with Moores Cancer Center at UC San Diego Health.

“These early results are really encouraging and intriguing;” Patel said. “We found a clear difference in response to treatment between the high-grade and low-grade forms of this cancer type. So tumor biology makes a difference. We don’t yet know why, but we’ve opened another treatment arm of the trial to patients with just high-grade neuroendocrine carcinoma to see if we see the same response to the immunotherapy combination.”

Drug combination

The DART trial, also known as S1609, is managed by SWOG; the cancer clinical trials group that is part of the National Cancer Institute’s National Clinical Trials Network (NCTN). DART features an innovative “basket” design which allows the testing of a single drug or drug combination in a variety of tumor types. DART currently tests the immunotherapy combination of ipilimumab and nivolumab in patients with 37 types of rare cancers, which together make up almost a quarter of all cancers diagnosed worldwide.

Results presented at the AACR Annual Meeting 2019 represent one of the 37 cohorts of DART; in which researchers enrolled 33 patients with neuroendocrine tumors. Of those 33 patients; 19 had high-grade disease. Most patients’ tumors were located in the gastrointestinal tract or the lungs. All patients received doses of ipilimumab every six weeks and doses of nivolumab every two weeks, and continue on the treatment for as long as their bodies respond to the drugs.

Doses of ipilimumab

Results showed that 42 % of patients with the high-grade form of neuroendocrine carcinomas saw their tumors shrink partially or completely after treatment; while none of the low-grade patients did. Because For all patients; 70% saw their cancer spread within six months. Patients survived a median of at least 11 months after treatment. Some patients are alive more than a year after treatment; and doctors continue to track their progress on the study drugs.
DART has enrolled over 550 patients since it opened in 2017 – an uncommon success for a rare cancers trial. The trial is open at over 800 hospitals, cancer centers; and community clinics across the U.S., widespread availability that is a unique feature of trials run through the NCTN and the NCI’s Community Oncology Research Program.