Nintedanib shows promise for nonpancreatic neuroendocrine tumors
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Nintedanib appeared safe and effective for the treatment of advanced nonpancreatic neuroendocrine tumors, according to results of a phase 2 study published in Cancer.
The agent slowed cancer progression for nearly 1 year, researchers noted.
“Midgut neuroendocrine tumors often secrete serotonin, which acts synergistically with PDGF and stimulates DNA synthesis in fibroblasts, leading to a dense fibrotic reaction and significant compromise in quality of life,” Renuka V. Iyer, MD, professor of oncology and section chief for gastrointestinal oncology at Roswell Park Comprehensive Cancer Center, as well as co-director of Roswell Park’s Liver and Pancreas Tumor Center, told Healio.
“A study in human gastroenteropancreatic neuroendocrine tumors showed that the FGF receptor [FGFR] was expressed in 70% of small intestine primary tumors. Fibroblast proliferation is an important disease driver in nonpancreatic neuroendocrine tumors that, in animal models, has been shown to be driven by serotonin through FGFR2, Iyer added.
“We therefore applied for and got a grant from the National Comprehensive Cancer Network to study nintedanib [Ofev, Boehringer Ingelheim], a targeted agent used in the treatment of idiopathic pulmonary fibrosis, in this disease so we could study whether targeting angiogenesis and FGFR could be of benefit.”
Researchers conducted the open-label, phase 2 study to evaluate nintedanib among 32 patients (median age, 65 years; range, 45-77) with advanced grade 1 or grade 2 nonpancreatic neuroendocrine tumors treated with a stable dose of somatostatin analogue. Twenty-seven patients (84%) experienced radiographic disease progression within 1 year before study enrollment.
All patients received 200 mg twice-daily nintedanib in 28-day cycles.
PFS at 16 weeks served as the primary endpoint.
Results among 30 patients evaluable for the primary endpoint showed PFS at 16 weeks of 83% (80% CI, 68-93), median PFS of 11 months (90% CI, 5.5-19.3) and median OS of 32.7 months (90% CI, 26 months to not reached).
Researchers reported a 1-year PFS rate of 41% (90% CI, 25-56) and 1-year OS rate of 90% (90% CI, 76-96).
Twenty-six patients (81%) achieved stable disease according to RECIST version 1.1 and one patient achieved partial response.
The most common adverse events were gastrointestinal, according to the researchers. One-quarter of patients developed thrombocytopenia, but cases appeared mild.
“Nintedanib was well-tolerated and delayed deterioration in quality of life. The baseline serotonin level had a strong, positive correlation with activated, but exhausted T cells,” Iyer said.
“An option that can slow disease progression for patients with neuroendocrine tumors, who often have metastatic disease at diagnosis, is exciting,” Iyer added. “At this time, we do not have plans for more studies with nintedanib, but we are looking at ways to target serotonin, as well as novel immunotherapy approaches using a survivin vaccine developed at our center, with grant support from [Neuroendocrine Tumor Research Foundation].”
For more information:
Renuka V. Iyer, MD, can be reached at Roswell Park Comprehensive Cancer Center, Elm and Carlton streets, Buffalo, NY, 14263; email: renuka.iyer@roswellpark.org.
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