Dose escalation of an Evans blue–modified radiolabeled somatostatin analog 177Lu-DOTA-EB-TATE in the treatment of metastatic neuroendocrine tumors

e15126 Background: Somastatin analogs (SSA), including octreotide and lanreotide, bind predominantly to somatostatin receptor (SSTR) 2 and form the foundation of treatment for symptomatic neuroendocrine tumors (NET). Pasireotide, a novel SSA with a broad binding affinity (SSTR 1-3 and 5), is being explored for treatment of NET. A phase 1 dose-escalation study (NCT01364415) of pasireotide long-acting release (LAR; starting dose of 80 mg) was designed to determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) and to characterize safety, tolerability, pharmacokinetics, and efficacy in pts with advanced NET. Methods: Pts with advanced, well- or moderately differentiated NET received pasireotide LAR beginning at a dose of 80 mg q28d. Successive cohorts will receive doses (up to 220 mg) guided by a Bayesian logistic regression model until MTD/RP2D is reached. Results: To date, 15 pts have been treated at 80 mg (n=6) and 120 mg (n=9). Median age is 59 (44-76) years. Primary tumor sites include small intestine (40%), pancreas (20%), and lung (13.3%). All pts received prior antineoplastic therapy; 93% received prior SSA. Median number of cycles of pasireotide was 6.68 (2-14) (1 cycle=28 days). 10 (67%) pts remain on treatment: 3 on 80 mg and 7 on 120 mg. 5 (33%) have discontinued (disease progression, 2 pts; withdrew consent, 2 pts; adverse event [AE], 1 pt). Median plasma concentrations of pasireotide increased with dose. No dose-limiting toxicities have been reported. Most frequent AEs were similar in both dose groups and included hyperglycemia (87%), diarrhea (53%), abdominal pain (47%), nausea (40%), anemia (33%), and fatigue (33%). Most AEs were mild/moderate. 2 pts (1 in each group) had grade 3 hyperglycemia. 4 (27%) and 2 (13%) pts had HbA1C increase from <6.5% at baseline to 6.5-<8% and ≥8%, respectively. 13 (87%) pts had radiographically stable disease as best response. More pts at 120 mg (50%) vs 80 mg (33%) achieved ≥50% reduction in chromogranin A. Conclusions: Pasireotide LAR up to 120 mg appears to be well tolerated in patients with advanced NET. The study is ongoing. Pasireotide represents a promising therapy for pts with NET. Clinical trial information: NCT01364415.

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Targeted radiopeptide therapy Re188-P2045 to treat neuroendocrine lung cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e20016 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e20016-e20016

Author(s):

Christopher Peter Adams ◽

Wasif M. Saif

Keyword(s):

Lung Cancer ◽

Image Analysis ◽

Cancer Patients ◽

Lung Tumor ◽

Somatostatin Receptor ◽

Receptor Expression ◽

Somatostatin Analog ◽

Receptor Subtype ◽

Lung Cancer Patients ◽

Radiolabeled Somatostatin Analog

e20016 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 up-regulated 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 cancer patients who over-express somatostatin receptors. Methods: In an open label, single arm study, refractory lung cancer patients to standard of care therapy were identified by image analysis using Rhenium Re 188 P2045, a radiolabeled somatostatin analog. 25 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 tumor lesions. 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&2. Conclusions: Rhenium Re 188 P2045, a radiolabeled somatostatin analog, may be used to both identify and treat lung 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 over express somatostatin receptor.

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