Peptide receptor radionuclide therapy combined with chemotherapy

Ziel/Aim:

Combination of therapies might enhance their therapeutic effect without significantly increasing the incidence of adverse events. However, there is sparse evidence regarding the survival after concomitant chemotherapy and peptide receptor radionuclide therapy (PRRT) with [¹⁷⁷Lu]Lu-octreotate in patients with neuroendocrine tumors (NET). We therefore explored the outcome of this combination of therapies.

Methodik/Methods:

Fifteen patients with rapidly progressive G2/G3 neuroendocrine tumors during chemotherapy or PRRT alone received a combination of PRRT and chemotherapy with temozolomide +/- capecitabine. All patients had somatostatin-receptor-positive metastases, proven by [⁶⁸Ga]Ga-DOTATOC-PET/CT. The metabolic acitivity was visualized in [¹⁸F]F-FDG-PET/CT. The imaging response was assessed according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) for computed tomography (CT) and PET Response Criteria in Solid Tumors (PERCIST 1.0) for [¹⁸F]F-FDG-PET/CT and/or [⁶⁸Ga]Ga-DOTATOC-PET/CT. The adverse events were classified according to Common Terminology Criteria for Adverse Events (CTCAE v5.0).

Ergebnisse/Results:

The cumulative administered activity of [¹⁷⁷Lu]Lu-octreotate was in median 22.4 GBq in a median of 3 combination cycles. Patients achieved a median progression-free survival (PFS) of 8.4 months and a median overall survival (OS) of 25.3 months. The observed clinical benefit (objective response and stable disease) according to RECIST was in 60% of patients and according to PERCIST in 38% of cases in [¹⁸F]F-FDG-PET/CT and 44% of cases in [⁶⁸Ga]Ga-DOTATOC-PET/CT. After the combination therapy one patient with rapid progression of liver metastases experienced liver failure grade 4 according to Common Toxicity Criteria (CTC). Four other patients (27%) had significantly elevated liver parameters (CTC grade 3).

Schlussfolgerungen/Conclusions:

In conclusion, the combination of PRRT with temozolomide +/- capecitabine showed a disease control according to different imaging modalities in 38%-60% of rapidly progressive NET after PRRT or chemotherapy alone failed. The OS in this severely pre-treated group of patients was nearly 25 months after combined PRRT and chemotherapy. The majority of patients did not experience any serious adverse events.