Early Experience of Rechallenge ¹⁷⁷Lu-PSMA Radioligand Therapy After an Initial Good Response in Patients with Advanced Prostate Cancer

Abstract

Our aim was to retrospectively evaluate the feasibility of rechallenge 177 Lu-prostate-specific membrane antigen ( 177 Lu-PSMA) radioligand therapy. Methods: Rechallenge radioligand therapy was defined as subsequent treatment with 177 Lu-PSMA after initial exposure with an excellent response followed by progression. Biochemical, radiographic, clinical antitumor response, and adverse events were analyzed. Prostate-specific antigen (PSA) progression-free survival (PFS) and overall survival were calculated. Results: Eight patients underwent a median of 2 (range: 1-4) cycles of rechallenge with 177 Lu-PSMA for imaging and therapy. A maximum PSA decrease of 50% was achieved in 3 patients (37.5%). Radiographic response was favorable in 3 patients, whereas 4 exhibited progressive disease. Eastern Cooperative Oncology Group performance status was stable during therapy in all patients. No grade 4 toxicity was noticed, and grade 3 toxicity occurred in 3 patients (37.5%). The median PSA-PFS and overall survival were 3.2 mo (95% confidence interval, 2.6-3.7 mo) and 14.0 mo (95% confidence interval, 6.2-21.8 mo), respectively. Conclusion: In a small patient cohort with an initial excellent response, 177 Lu-PSMA rechallenge is still active, with lower efficacy and higher toxicity. Lu-PSMA Radioligand Therapy After an Initial 177 Early Experience of Rechallenge http://jnm.snmjournals.org/content/60/5/644 This article and updated information are available at: http://jnm.snmjournals.org/site/subscriptions/online.xhtml Information about subscriptions to JNM can be found at: http://jnm.snmjournals.org/site/misc/permission.xhtml

The 68Ga/177Lu-theragnostic concept in PSMA-targeting of metastatic castration–resistant prostate cancer: impact of post-therapeutic whole-body scintigraphy in the follow-up

“…Yordanova et al [16] recently reported a clinical benefit in 30 177 Lu-PSMA-617 re-treated patients with a median OS of 25 months versus 9 months in patients who received only one 177 Lu-PSMA-617 treatment period, each period consisting of several treatment cycles. Similar beneficial results were reported for 177 Lu-PSMA-I&T re-treatment by Grubmüller et al [17] and Gafita et al [18]. Basically, these retrospective analyses raise the question whether higher activities than 6 GBq of 177 Lu-PSMA-617 would fit more appropriate as Grade 4 toxicity is rare, even in rechallenged patients, with reasonable efficacy.…”

“…The currently most commonly used Reponse Evaluation Criteria In Solid Turmors (RECIST) [2] are based on cross-sectional abdominopelvic imaging together with bone scintigraphy and PSA serum levels. 68 Ga-PSMA-11 PET/CT revealed a higher probability for a positive PET-finding in patients with low PSA values (≤ 0.5 ng/ml) than any other imaging modality including 18 F-choline PET/CT [3], which can substantially influence the clinical management. In fact, 68 Ga-PSMA-11 provides more accurate assessment than conventional imaging [4] and can also be superior to 18 F-sodium fluoride PET/CT for the evaluation of bone metastases in response to 223 Ra-chloride therapy [5].…”

Genetic signature of prostate cancer mouse models resistant to optimized hK2 targeted α-particle therapy

“…Interestingly, these findings bear a resemblance to the genetic changes reported in glucocorticoid receptor-driven enzalutamide resistance (8). While the underlying radiobiological mechanisms instigating PSMA down-regulation during treatment and in recurrent tumors could be different, these observations could potentially explain the reduced treatment efficacy noted upon repeated PSMA-targeted RIT and radioligant therapy (5,35,36). Although preclinical models have limitations, the present outcome demonstrates efficacy of serial [ 225 Ac]hu11B6 treatment in a mouse model; relapsing tumors in mice express abundant levels of hK2 (KLK2) (SI Appendix, Fig.…”

Factors predicting biochemical response and survival benefits following radioligand therapy with [177Lu]Lu-PSMA in metastatic castrate-resistant prostate cancer: a review

“…Recently, a repeated course of [ 177 Lu]Lu-PSMA RLT is being administered to some patients with a prior excellent response [44,45] and authors are investigating the prognostic factors [29]. They showed that rechallenge therapy is safe.…”