Objectives: Peptide receptor radionuclide therapy (PRRT) with radiolabeled somatostatin analogues is a promising treatment for patients with inoperable, well to moderately differentiated metastatic neuroendocrine tumors (NETs). In continuation of our novel study with the radionuclide lutetium Lu, we now present further results of Lu DOTATATE therapy in managing NETs and other somatostatin receptor-expressing tumors in a larger and more diverse patient group.
Patients and methods: One hundred forty-four consecutive patients (85 men and 59 women; age range, 11-87 years; mean age, 58.5 years) with histologically confirmed NET were enrolled. One hundred forty-three patients received at least 1 cycle of treatment. Among them, 132 were deemed evaluable by having at least 1 cycle of treatment and a posttreatment MRI or CT scan for assessment based on modified Response Evaluation Criteria in Solid Tumors. Response to therapy was evaluated in terms of progression-free survival, overall survival, as well as radiologic, biochemical, and clinical responses. Further, analysis of symptoms was reviewed during therapy and also in subsequent follow-ups for safety evaluation. Renal, gastrointestinal (GI), hepatic, and hematological adverse events were evaluated using National Cancer Institute common toxicities criteria V4.03, through full blood panels, as well as consultation with patients for any symptoms and/or adverse events.
Results: As of July 2016, median progression-free survival was about to be reached. Of 28 patients who have completed Lu DOTATATE therapy (completion of 4 or more cycles of treatment and all designated follow-ups), no patient showed complete response (CR), 8 patients (28.57%) showed partial response (PR), 16 patients (57.14%) showed stable disease (SD), and progressive disease (PD) was observed in 4 patients (14.28%). The objective response rate (CR + PR) of this group was 28.57% (n = 8) with a cumulative disease control (CR + PR + SD) of 85.71% (n = 24).Among 132 evaluable patients, assessment of treatment response using modified Response Evaluation Criteria in Solid Tumors criteria revealed CR in none of the patients, PR in 12 patients (9.09%), SD in 66 patients (50%), whereas PD, which included patients who passed away, was observed in 54 patients (40.90%), yielding an objective response rate of 9.09% (n = 12) and a cumulative disease control rate of 59.09% (n = 78).Symptoms including abdominal pain, diarrhea, flushing, and fatigue improved in over 50% of the patients, whereas weight loss improved in 28.26% of the patients. No grade 3 or grade 4 renal toxicities were found, though eleven grade 3 and five grade 4 hematological as well as three grade 3 hepatotoxicities were reported. Grade 3 hematotoxicity lasted an average of 2.7 months, and grade 4 lasted for only 0.9 months, whereas grade 3 hepatotoxicity lasted an average of 3.1 months.
Conclusions: Lu-octreotate peptide receptor radionuclide therapy has shown promising potential as a safe and effective targeted therapy in inoperable, well to moderately differentiated metastatic neuroendocrine cancers. The results of the multicenter randomized clinical trial conducted in United States and Europe are concordant with current study.