Lutetium-177-PSMA therapy for recurrent/metastatic salivary gland cancer: a prospective pilot study
Niels J. van Ruitenbeek, Maike J.M. Uijen, C.M.L. Driessen, Steffie M. B. Peters, Bastiaan M. Privé, Adriana C. H. van Engen–van Grunsven, Mark Konijnenberg, Martin Gotthardt, James Nagarajah, Carla M.L. van Herpen
Abstract
There is an urgent need for novel systemic therapies for recurrent/systemic salivary gland cancer, as current treatment options are scarce.[ 68 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 [ 177 Lu]Lu-PSMA-I&T treatment in AdCC and SDC patients in a prospective pilot study.Methods: 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 SUVmax on [ 68 Ga]Ga-PSMA-11 PET/CT above liver SUVmean.Patients were planned to receive four cycles ~ 7.4 GBq [ 177 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.Results: 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 0.001-0.63Gy/GBq).Conclusions: [ 177 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, [ 177 Lu]Lu-PSMA-I&T appears unfeasible due to insufficient PSMA uptake.