Lutetium-177-PSMA therapy for recurrent/metastatic salivary gland cancer: a prospective pilot study

• Published in: Theranostics Vol. 14; no. 14; pp. 5388 - 5399
• Main Authors: van Ruitenbeek, Niels J, Uijen, Maike J M, Driessen, Chantal M L, Peters, Steffie M B, Privé, Bastiaan M, van Engen-van Grunsven, Adriana C H, Konijnenberg, Mark W, Gotthardt, Martin, Nagarajah, James, van Herpen, Carla M L
• Format: Journal Article
• Language: English
• Published: Australia Ivyspring International Publisher 01-01-2024
• Subjects: Adult; Aged; Antigens, Surface; Carcinoma, Adenoid Cystic - diagnostic imaging; Carcinoma, Adenoid Cystic - drug therapy; Carcinoma, Adenoid Cystic - radiotherapy; Carcinoma, Ductal - drug therapy; Carcinoma, Ductal - radiotherapy; Carcinoma, Ductal - therapy; Female; Glutamate Carboxypeptidase II; Humans; Lutetium - therapeutic use; Male; Middle Aged; Neoplasm Recurrence, Local; Pilot Projects; Positron Emission Tomography Computed Tomography; Prospective Studies; Radioisotopes - therapeutic use; Radiopharmaceuticals - therapeutic use; Research Paper; Salivary Gland Neoplasms - drug therapy; Salivary Gland Neoplasms - pathology; Salivary Gland Neoplasms - radiotherapy; Salivary Gland Neoplasms - therapy; Salivary duct carcinoma; Lu-PSMA therapy; Salivary gland cancer; Adenoid cystic carcinoma; Prostate-specific membrane antigen
• ISSN: 1838-7640; 1838-7640
• DOI: 10.7150/thno.99035

There is an urgent need for novel systemic therapies for recurrent/systemic salivary gland cancer, as current treatment options are scarce. [
Ga]Ga-PSMA-11 PET/CT revealed relevant uptake of prostate-specific membrane antigen (PSMA) in adenoid cystic carcinoma (AdCC) and salivary duct carcinoma (SDC). Therefore, we assessed the safety, feasibility, efficacy and radiation dosimetry of [
Lu]Lu-PSMA-I&T treatment in AdCC and SDC patients in a prospective pilot study.
This single-center, single-arm study intended to include 10 recurrent/metastatic AdCC patients and five recurrent/metastatic SDC patients. AdCC patients could only participate in case of progressive and/or symptomatic disease. Patients required ≥ 1 lesion ≥ 1.5 cm with an SUV
on [
Ga]Ga-PSMA-11 PET/CT above liver SUV
. Patients were planned to receive four cycles ~ 7.4 GBq [
Lu]Lu-PSMA-I&T. In case of progressive disease per RECIST 1.1 at mid-treatment evaluation after two cycles, treatment was discontinued. Safety was the primary endpoint. Secondary endpoints included objective response rate (ORR), tumor- and organ-absorbed radiation doses and progression-free survival.
After screening, 10 out of 15 (67%) AdCC and two out of 10 (20%) SDC patients were eligible. Two patients (17%) demonstrated grade 3 treatment-related toxicity: lymphocytopenia (8%) and hyponatremia (8%). No dose-limiting toxicities occurred. In the AdCC cohort, six patients (60%) completed the four treatment cycles. Due to progressive disease, treatment was discontinued after two cycles in three patients (30%) and after one cycle in one patient (10%). No objective responses were observed (ORR: 0%). Three AdCC patients (30%) showed stable disease ≥ 6 months (7, 17 and 23 months). None of the two SDC patients completed the treatment: one patient deteriorated after the first cycle, while the other had progressive disease after two cycles. The high screen failure rate due to insufficient PSMA uptake resulted in premature closure of the SDC cohort. Dosimetry revealed low tumor-absorbed doses (median 0.07 Gy/GBq, range 0.001-0.63 Gy/GBq).
[
Lu]Lu-PSMA-I&T in AdCC and SDC patients was safe and generally well-tolerated. However, efficacy was limited, likely due to low tumor-absorbed doses. For SDC, [
Lu]Lu-PSMA-I&T appears unfeasible due to insufficient PSMA uptake.