Immunotherapy of Ipilimumab and Nivolumab in Patients with Advanced Neuroendocrine Tumors: A Subgroup Analysis of the CA209-538 Clinical Trial for Rare Cancers.

2020-09

Klein, Oliver

Kee, Damien

Markman, Ben

Michael, Michael

Underhill, Craig

Carlino, Matteo S

Jackett, Louise A

Lum, Caroline

Scott, Clare

Nagrial, Adnan

Behren, Andreas

So, Jane Y

Palmer, Jodie

Cebon, Jonathan S

Journal Article

0000-0002-4685-1666

0000-0002-0593-2662

0000-0001-9533-4588

0000-0002-3689-5956

0000-0001-5329-280X

0000-0002-3221-8552

0000-0002-8964-0965

0000-0002-3898-950X

10.1158/1078-0432.CCR-20-0621

Combination immunotherapy with anti-CTLA-4 and anti-PD-1 blockade has demonstrated significant clinical activity across several tumor types. Neuroendocrine tumors (NET) are a heterogeneous group of rare tumors with limited treatment options. CA209-538 is a clinical trial of combination immunotherapy with ipilimumab and nivolumab in rare cancers, including advanced NETs. CA209-538 is a prospective multicenter clinical trial in patients with advanced rare cancers. Patients received treatment with nivolumab at a dose of 3 mg/kg and ipilimumab at 1 mg/kg every three weeks for four doses, followed by nivolumab 3 mg/kg every two weeks and continued for up to 96 weeks, until disease progression or the development of unacceptable toxicity. Response was assessed every 12 weeks by RECIST 1.1. The primary endpoint was clinical benefit rate (CBR; complete remission + partial remission + stable disease). Twenty-nine patients with advanced NETs received treatment. Three (10%) patients had low-, 13 (45%) had intermediate-, and 13 (45%) had high-grade tumors; lung was the most common primary site (39%). The objective response rate was 24% with a CBR of 72%; 43% of patients with pancreatic neuroendocrine neoplasms (NEN), and 33% of patients with atypical bronchial carcinoid achieved an objective response. The median progression-free survival was 4.8 months [95% confidence interval (CI): 2.7-10.5] and overall survival was 14.8 months (95% CI: 4.1-21.3). Immune-related toxicity was reported in 66% of patients with 34% experiencing grade 3/4 events. Combination immunotherapy with ipilimumab and nivolumab demonstrated significant clinical activity in subgroups of patients with advanced NETs including patients with atypical bronchial carcinoid and high-grade pancreatic NENs.

link

Clinical Cancer Research 2020; 26(17): 4454-4459

Clinical Cancer Research