Abstract
Abstract Background: Despite the recent success of checkpoint inhibitors, there continues to be a significant medical need for lung cancer therapies that can be directed to the patients most likely to respond. Somatostatin receptor subtype 2 (SSTR2) is the most widely upregulated subtype in both small and non-small cell lung cancers and is also expressed in tumoral (but not mature) blood vessels. Peptide-targeted radiotherapy has advantages over traditional targeted therapies in that targeted tumor cells as well as surrounding cancer cells and supporting stroma are selectively killed. This study was conducted to determine the ability of Rhenium Re 188 P2045, a radiolabeled somatostatin analog specific for SSTR2 to both image (to select the most appropriate patients) and treat lung and neuroendocrine cancer patients who overexpress somatostatin receptors. Methods: In an open-label, single-arm study, refractory lung cancer and metastatic neuroendocrine patients to standard-of-care therapy were identified by image analysis using Rhenium Re 188 P2045, a radiolabeled somatostatin analog. Twenty-five patients received the imaging dose of 10uCi of Re188 and 265ng of peptide by intravenous injection. Three patients were selected based on high SSTR expression levels to receive 30uCi of Re188 P2045 as a therapeutic dose 14 days after imaging. Patients were followed for 8 weeks post treatment. Results: The imaging study revealed a high density of expression of the somatostatin receptor in the lungs of patients. Patients in the imaging and therapeutic treatment groups reported no adverse advents or signs of toxicity. The image analysis using Re188 P2045 was compared to CT images and demonstrated accurate detection of lung and neuroendocrine tumor lesions. The patients who received R188 P2045 at the therapeutic dose had a 25% reduction in tumor mass based on image analysis versus typical results of stable disease from standard of care. The images obtained using Re188 P2045 were of sufficiently high quality to enable identification of receptor expression at the tumor site as shown in Figures 1 and 2 (figures not available). Conclusions: Rhenium Re 188 P2045, a radiolabeled somatostatin analog, may be used to both identify and treat lung and neuroendocrine cancer tumors. The ability to image and dose patients with the same targeted molecule enables a personalized medicine approach, and this highly targeted patient therapy may significantly improve treatment of tumors that overexpress somatostatin receptors. Citation Format: Chris Adams, Ajit Shinto, Wasif Saif. Targeted radiopeptide therapy re188-P2045 to treat neuroendocrine lung cancer [abstract]. In: Proceedings of the Fifth AACR-IASLC International Joint Conference: Lung Cancer Translational Science from the Bench to the Clinic; Jan 8-11, 2018; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(17_Suppl):Abstract nr B06.
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