IMMUNOTHERAPY FOR NEUROENDOCRINE TUMORS

Patients with fast-growing non-pancreatic neuroendocrine tumors may respond to combination therapy with ipilimumab plus nivolumab, according to findings within the Dual Anti-CTLA-4 & Anti-PD-1 blockade in Rare Tumors (DART) trial.

The non-randomized DART trial "has served an unmet need to bring an immunotherapy clinical trial to patients with rare cancers," Dr. Razelle Kurzrock told Reuters Health by email,

"In the first read-out of the trial," Dr. Kurzrock of UCSD Moores Cancer Center, in La Jolla, California, said, "we found that high-grade neuroendocrine cancers had a response rate of about 44%, suggesting that the combination of nivolumab and ipilimumab is an important treatment option for these difficult-to-manage cancers."

In a paper in Clinical Cancer Research, the investigators note that they aim to use the immunotherapy combination in 53 classes of rare cancers as part of DART. At present, the trial is enrolling patients with 12 different cancer types.

The current study examined the non-pancreatic neuroendocrine cohort, which consisted of 32 patients; 18 (56%) had high-grade disease and the most common primary sites were gastrointestinal (47%) and pulmonary (19%).

Of those with high-grade neuroendocrine carcinoma, almost half (44%) showed an overall response, whereas none of the remaining 14 patients with low- or intermediate-grade tumors did.

The overall six-month progression-free survival (PFS) was 31%. In high-grade disease, it was 44% and in low-grade disease, 14%. The median PFS is four months and the median overall survival is 11 months, with ongoing responses.

Coauthor Dr. Sandip Patel, also of UCSD Moores Cancer Center, told Reuters Health by email, "Our results suggest that ipilimumab and nivolumab may have activity against high-grade neuroendocrine neoplasms, and no benefit in low- to intermediate-grade neuroendocrine neoplasms."

"We are currently confirming these results within the study with a dedicated high-grade neuroendocrine cohort, which we hope may represent a new treatment option for this very aggressive rare tumor," he concluded.

The trial is supported in part by Bristol-Myers Squibb, which sells ipilimumab as Yervoy. Dr. Patel and other authors have relationships with the company.

SOURCE: https://bit.ly/2TCuA4H Clinical Cancer Research, online 22 February, 2020.