Potential of dual checkpoint blockade shown for neuroendocrine tumors
medwireNews: Patients with high-grade neuroendocrine tumors (NETs) may benefit from combined treatment with the PD-1 inhibitor nivolumab and the anti-CTLA-4 agent ipilimumab, indicate phase II results.
Data from the neuroendocrine cohort of the basket DART (Dual Anti-CTLA-4 and Anti-PD-1 Blockade in Rare Tumors) trial, which did not include individuals with pancreatic NETs, were presented at the AACR Annual Meeting 2019, held in Atlanta, Georgia, USA.
A total of 32 patients with NETs, most commonly originating in the gastrointestinal tract (47%) or lung (19%), were given nivolumab 240 mg every 2 weeks alongside ipilimumab 1 mg/kg every 6 weeks until progression, unacceptable toxicity, or withdrawal of consent.
As reported by Sandip Patel (UCSD Moores Cancer Center, La Jolla, California, USA), the overall response rate (ORR) in the full cohort was 25%, rising to 44% for the 18 patients with high-grade tumors; none of the participants with intermediate- or low-grade disease achieved a response.
“[O]ne 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,” commented Patel in a press release.
The clinical benefit rate – which included patients with a complete or partial response or stable disease for more than 6 months – was 30% in the total cohort and 44% in the group with high-grade NETs.
The 6-month progression-free survival rate was 31% and median overall survival was over 11 months, which compare favorably with the historic values of around 10% and approximately 3 months, respectively, said Patel.
He added that the combination was well tolerated, with adverse events of grade 3–4 occurring in 37.5% of participants. The most common of these were liver function abnormalities (9.0%) and colitis (6.0%), and there were no cases of pneumonitis or grade 5 toxicities.
The presenter concluded that the combination shows “promising signs of benefit in high-grade carcinoma,” but noting the single-arm nature of the cohort and the small number of patients, he said that confirmatory analyses are underway within the DART trial.
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