Peptide Receptor Radionuclide Therapy as First Line Systemic Treatment in Advanced Inoperable/Metastatic Neuroendocrine Tumours

Objectives: Neuroendocrine tumours (NETs) are a rare group of malignancies that have shown an increased global burden over the recent decades. Treatment of advanced inoperable/metastatic NETs poses a therapeutic challenge with limited treatment options. Although, somatostatin analogues are currently considered as the first line therapy for advanced NETs, their practical use is often limited owing to their exorbitant costs. Peptide Receptor Radionuclide Therapy (PRRT), being specific in targeting the somatostatin receptors, is a promising and viable option in this setting. In this study, we intended to evaluate the role of PRRT as the first line systemic therapy in advanced inoperable/metastatic NETs.

Methods: This was a retrospective, single centre, single arm interventional study. Data of consecutive patients of advanced inoperable/metastatic NETs having initiated treatment with 177Lu - DOTATATE between September 2012 and August 2019, were collected and analysed. Additionally, as part of our institutional protocol, oral capecitabine 1250 mg/m2 was also administered orally as a radiosensitizer from days 0-14 of each PRRT cycle. Radiological response was assessed using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Biochemical response was assessed using serum chromogranin levels. Treatment related toxicity was evaluated using Common Terminology Criteria for Adverse Events (CTCAE), version 5.0.

Results: 45 patients (median age 50 years, range 14 - 72 years) with advanced inoperable/metastatic NETs received a median cumulative dose of 27 GBq (range 13.3 - 41.3 GBq, over 2 - 7 cycles) ¹⁷⁷Lu - DOTATATE and 1250 mg/m² capecitabine from days 0 to 14 of each PRRT cycle. Three patients were lost to follow-up, two had non-measurable lesions on CT and radiological response using RECIST 1.1 could be assessed in 40 patients. 12/40 (30%) patients showed a partial response while stable disease was observed in 22/40 (55%) patients. Disease progression was limited to only 6/40 (15%) patients. Biochemical response could be assessed in 15 patients with 7 patients (47%) showing a ≥50% decline in serum chromogranin A levels. Treatment related adverse effects were minimal with grade 3/4 anaemia, leucopenia, neutropenia and hepatotoxicity observed in 2%, 2%, 4% and 4% of the patients respectively.

Conclusions: Our results indicate the efficacy and safety of first-line PRRT in advanced NETs with an observed objective response rate of 30% and disease control rate of 85% and no significant treatment related toxicity. Added benefit with PRRT was observed in comparison to the published outcomes with somatostatin analogues. Being a relatively cost-effective agent, our results with first line PRRT are encouraging. Larger RCTs, comparing both the modalities in treatment naïve patients, are required to identify the definite sequence of treatment options for these patients.