Abstract
IntroductionThe impact of prior therapies, especially chemotherapy, on overall survival (OS) in patients with castration-resistant prostate cancer (CRPC) receiving [177Lu]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 177Lu-PSMA-617.Materials and methodsThe 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 [177Lu]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.ResultsThe 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.ConclusionIn the present multicenter analysis, chemotherapy-naïve mCRPC patients receiving [177Lu]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.
Highlights
The impact of prior therapies, especially chemotherapy, on overall survival (OS) in patients with castration-resistant prostate cancer (CRPC) receiving [177Lu]Lu-Prostate-specific membrane antigen (PSMA)-617 therapy has been the subject of controversy
The study populations targeted in this study were metastatic CRPC (mCRPC) patients who underwent radioligand therapy with 177LuPSMA-617 with at least a 6-month follow-up from the time of the first cycle or who died within this time period
Inclusion criteria Castration-resistant metastatic prostate cancer Age > 18 years radioligand therapy (RLT) using 177Lu-PSMA-617 Documented progressive disease prior to the first cycle according to prostate-specific antigen (PSA) and/or imaging History of therapy with abiraterone or enzalutamide or both, or documented progressive disease under ongoing therapy with one of these agents PSMA-positive metastases Eastern Cooperative Oncology Group (ECOG) 0–2 GFR > 40 mg/dl Have a follow-up at least 6 months from the time of the first cycle, or the patient died within this time
Summary
Four-hundred sixteen mCRPC patients with a median age of 71.9 years (range 43–90) were included. The median interval between the last application of radium-223 and the first cycle of 177Lu-PSMA-617 therapy was 3.9 months (range 1–36.4 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 (95% CI 9.05– 12.76) and 8.9 months (95% CI 6.9–10.9). The OS was significantly shorter than in patients without any prior chemotherapy with a median OS of 14.6 months (95% CI 10.3–18.4) (Fig. 1). The median OS of patients with a PSA decline of less than 50% as well as with a decline ≥ 50% was significantly longer than patients with a rising PSA after the first cycle.
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