Influence of short‐term dexamethasone on the efficacy of <sup>177</sup>Lu‐PSMA‐617 in patients with metastatic castration‐resistant prostate cancer
Thorsten Derlin, Jan M Sohns, Sebastian Schmuck, Christoph Henkenberens, Christoph A. J. von Klot, Tobias L. Roß, Frank M. Bengel
Abstract
Abstract Background and Aim Corticosteroids alone or in combination therapy are associated with favorable biochemical responses in metastatic castration‐resistant prostate cancer (mCRPC). We speculated that the intermittent addition of dexamethasone may also enhance the antitumor effect of radioligand therapy (RLT) with 177 Lu‐prostate‐specific membrane antigen (PSMA)‐617. Patients and Methods Seventy‐one patients with mCRPC were treated with 1 to 5 cycles of 177 Lu‐PSMA‐617 (6.0‐7.4 GBq per cycle) at 6 to 8 weeks intervals. Based on the clinical decision (eg, in the case of vertebral metastases), 56% of patients received 4 mg of dexamethasone for the first 5 days of each cycle. Biochemical response rates, PSA decline and progression‐free survival (PFS) were analyzed after one, three, and five cycles of RLT. Results PSA response rates were not significantly different between patients receiving 177 Lu‐PSMA‐617 plus dexamethasone and those receiving 177 Lu‐PSMA‐617 alone after one, three, and five cycles (33% vs 39%, P = .62; 45% vs 45%, P = 1.0; and 38% vs 42%, P = .81). However, there was a nonsignificant trend for a more pronounced PSA decline in patients with bone metastases receiving adjunct dexamethasone (−21% ± 50% vs +11% ± 90%, P = .08; −21% ± 69% vs +22% ± 116%, P = .07; −13% ± 76% vs +32% ± 119%, P = .07). Median PFS tended to be longer in patients with bone metastases receiving 177 Lu‐PSMA‐617 plus dexamethasone (146 vs 81 days; hazard ratio: 0.87 [95% confidence interval: 0.47‐1.61]; P = .20). Multiple regression analysis showed that age ( P = .0110), alkaline phosphatase levels ( P = .0380) and adjunct dexamethasone ( P = .0285) were independent predictors of changes in PSA in patients with bone metastases. Conclusions We observed high response rates to 177 Lu‐PSMA‐617 RLT in men with mCRPC. The short‐term addition of dexamethasone to 177 Lu‐PSMA‐617 had no striking antitumor effect but might enhance biochemical responses in patients with bone metastases. Future trials are warranted to test this hypothesis in a prospective setting.