Prior therapies as prognostic factors of overall survival in metastatic castration-resistant prostate cancer patients treated with [177Lu]Lu-PSMA-617. A WARMTH multicenter study (the 617 trial)

Abstract

Introduction The impact of prior therapies, especially chemotherapy, on overall survival (OS) in patients with castration-resistant prostate cancer (CRPC) receiving [ 177 Lu]Lu-PSMA-617 therapy has been the subject of controversy. Therefore, WARMTH decided to plan a multicenter retrospective analysis (the “617 trial”) to evaluate response rate and OS as well as the impact of prior therapies on OS in more than 300 patients treated with 177 Lu-PSMA-617. Materials and methods The data of 631 metastatic CRPC (mCRPC) patients from 11 different clinics were evaluated. According to the inclusion and exclusion criteria, all patients had to have received at least abiraterone or enzalutamide prior to [ 177 Lu]Lu-PSMA-617 therapy. The patients were divided into three groups: patients who had received prior chemotherapy, patients who avoided chemotherapy, and patients for whom a chemotherapy was contraindicated. Results The analysis included the data of 416 patients, with a median age of 71.9 years. At the time of analysis, 87 patients (20,9%) were still alive. A total of 53.6% of patients had received both abiraterone and enzalutamide; 75.5% and 26.4% had a history of chemotherapy with docetaxel and cabazitaxel, respectively. A total of 20.4% had had Ra-223. The median OS was 11.1 months. Prior chemotherapy, the existence of bone and liver metastases, as well as Eastern Cooperative Oncology Group (ECOG) status, were significant prognosticators of worse overall survival in both univariate and multivariate analyses. Patients without any prior chemotherapy showed a significantly longer OS (14.6 months). The median OS in patients who received one or two lines of chemotherapy with docetaxel or docetaxel followed by cabazitaxel, respectively, was 10.9 months and 8.9 months. There was no difference in OS between patients who had not received chemotherapy and patients for whom chemotherapy was contraindicated. The other prior therapies did not have any significant impact on OS. Conclusion In the present multicenter analysis, chemotherapy-naïve mCRPC patients receiving [ 177 Lu]Lu-PSMA-617 therapy had a significantly longer OS than patients with a history of chemotherapy. This remained independent in the multivariate analysis besides presence of bone and liver metastases as negative prognosticators for survival, whereas an ECOG of 0–1 is associated with a longer OS. Electronic supplementary material The online version of this article (10.1007/s00259-020-04797-9) contains supplementary material, which is available to authorized users.

Prognostic implications of dual tracer PET/CT: PSMA ligand and [18F]FDG PET/CT in patients undergoing [177Lu]PSMA radioligand therapy

“…This is in line with previous findings demonstrating that the presence of visceral metastases, especially liver metastases, results in poorer survival [20] [21]. ECOG status has also been identified as a prognosticator of OS before [22]. The extent of metastases on PSMA ligand PET/CT was only a significant prognostic marker on univariate analysis.…”

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

“…Although the prognosis is generally favorable [2], the treatment of PC is challenging in the cases of metastatic castration-resistant prostate cancer (mCRPC) [3]. The prostate-specific membrane antigen (PSMA) is a transmembrane protein and highly expressed in PC cells [1,4]. Radioligands targeting PSMA are promising agents for the imaging and treatment of PC patients [1,[5][6][7].…”

Improving quality of life in patients with metastatic prostate cancer following one cycle of 177Lu-PSMA-617 radioligand therapy: a pilot study

“…The aim of our study was analysis of early changes in quality of life in prostate cancer patients after the first cycle of 177 Lu-PSMA-617 therapy and its association with alterations in PSA. Recent analyses have proven the efficacy of PSMA treatment compared to standard treatment for metastatic castration-resistant prostate cancer (mCRPC) [3,[11][12][13][14][15]. The most recent systematic review and meta-analysis [11] covering all studies published up to August 2018 on the efficacy and safety of 177 Lu-PSMA-617 RLT included 17 original articles on altogether 744 patients.…”

“…The latest published papers about radioligand therapy (RLT) with 177 Lu-PSMA-617 showed that the treatment is well tolerated and has a low toxicity profile [1,2]. First results have indicated that this therapy further has a positive impact on the prolongation of overall survival (OS) [1,3]. Apart from a prolongation of OS and low toxicity profile the best clinical outcome for the patients would be achieved when a new therapy has also a positive influence on quality of life (QoL).…”