In a French phase II trial (GCO-001-NIPINEC) reported in the Journal of Clinical Oncology, Walter et al found that nivolumab plus ipilimumab showed some activity in patients with advanced gastroenteropancreatic (GEP) or lung large-cell neuroendocrine carcinoma (NEC) after failure of platinum-based chemotherapy.
Study Details
The multicenter open-label study enrolled 169 evaluable patients with advanced large- and small-cell GEP-NEC and large-cell lung NEC refractory to platinum-based chemotherapy. Patients were randomly assigned between December 2018 and March 2021 to receive second- or third-line treatment with nivolumab at 3 mg/kg every 2 weeks with (n = 86) or without (n = 83) ipilimumab at 1 mg/kg every 6 weeks for 2 years or until disease progression or unacceptable toxicity. Primary tumor locations included lung (50%), colorectal (15%), gastroesophageal (14%), and pancreatic (13%) sites. The primary endpoint of the study was objective response rate at 8 weeks.
Key Findings
The objective response rate at 8 weeks was 7.2% (95% confidence interval [CI] = 2.7%–15.1%) in the nivolumab group and 14.0% (95% CI = 7.4%–23.1%) in the nivolumab plus ipilimumab group. Disease control rates at 8 weeks were 38.6% and 31.4%, respectively.
The best objective response rates were 9.6% in the nivolumab group and 20.9% in the nivolumab plus ipilimumab group, with median response durations of 12.2 and 12.0 months. Median progression-free survival was 1.8 and 1.9 months; median overall survival was 6.2 and 6.1 months, with 1-year rates of 33.7% and 32.6%.
The most common grade 3 or 4 adverse events in the nivolumab plus ipilimumab group were asthenia (13%), gamma-glutamyl transferase increase (10%), alkaline phosphatase increase (9%), dyspnea (7%), and anemia (6%). One treatment-related death occurred in the nivolumab group (due to encephalitis).
The investigators concluded: “Nivolumab-ipilimumab could be a second-/third-line treatment option for patients with NECs. However, given the limited magnitude of benefit, studies are warranted to evaluate its use earlier and/or associated with chemotherapy.”
Thomas Pierre Walter, MD, PhD, of Hospices Civils de Lyon, Cancer Research Center of Lyon, Lyon, France, is the corresponding author for the Journal of Clinical Oncology article.
DISCLOSURE: The study was supported by Bristol-Myers Squib. For full disclosures of the study authors, visit ascopubs.org.
