Lu177 as a promising new therapy for metastatic prostate cancer

Radionuclide therapy directed towards prostate-specific membrane antigen (PSMA) showed promising results in men with docetaxel-treated metastatic castration-resistant prostate cancer (mCRPC) [1]. A phase 2 trial comparing the use of radionuclide therapy using lutetium-177 (Lu177) with chemotherapy using cabazitaxel found greater reductions in prostate-specific antigen (PSA) levels, longer periods of progression-free survival (PFS), and greater tumour objective response rates (ORR) in patients treated with Lu177.

The cell surfaces of prostate cancers strongly express PSMA - even more so in cases of mCRPC. For this reason, PSMA is used both for imaging prostate cancer and as a target for radionuclide therapy.

Dr Michael Hofman (Peter MacCallum Cancer Centre, Australia) discussed the open-label, randomised, multicentre, phase 2 TheraP trial (NCT03392428), which assessed the activity and safety of Lu177-labelled PSMA (LuPSMA) for the treatment of mCRPC [1]. Included men with docetaxel-treated mCRPC and high PSMA expression (n=200) were randomised to receive either ≤6 cycles of radionuclide therapy with LuPSMA or ≤10 cycles of chemotherapy with cabazitaxel.

The primary outcome measure was PSA response rate, defined as the proportion of participants in each group with a ≥50% reduction in PSA from baseline. In the Lu177 group, 65 men (66%) achieved this outcome, compared with 37 men (37%) in the cabazitaxel group (see Figure).

Figure: Primary outcome measure of progression-free survival [1]



CI, confidence interval; HR, hazard ratio; LuPSMA, lutetium-177-labelled prostate-specific membrane antigen.

Secondary outcome measures included 9 parameters and were analysed after a median follow-up period of 18.4 months. PFS was 19% (95% CI 12–27%) in the radiotherapy group versus 3% (95% CI 1–9%) in the cabazitaxel group (HR 0.63; 95% CI 0.46–0.86; P=0.003; 173 events). Comparable results were found for both radiographic PFS (HR 0.64; 95% CI 0.46–0.88; P=0.007; 160 events) and PSA-PFS, which was defined as the time from randomisation to PSA progression (HR 0.60; 95% CI 0.44–0.83; P=0.002; 172 events). ORR was 49% (95% CI 33–65%) in the Lu177 group and 24% (95% CI 11–38%) in the chemotherapy group (P=0.019). Overall survival will be monitored for 4 years; this data is not yet available since the study only reached its completion date January 2021. To date, 90 deaths are reported. Regarding pain outcomes, 60% of participants in the radiotherapy arm and 43% of participants in the cabazitaxel arm reported pain (RR 1.42; 95% CI 0.84–4.48; P=0.10) at the end of follow-up.

Adverse events (AEs) were monitored from the time of first study dose to 12 weeks after treatment completion. Fewer grade 3 and 4 AEs occurred in the Lu177 group than in the cabazitaxel group (33% vs 53%). The top 3 grade 3 or 4 AEs experienced in the Lu177 group were thrombocytopenia, anaemia, and fatigue; in the cabazitaxel group, they were neutropenia, anaemia, and diarrhoea.

Concerning health-related quality of life outcomes, global health status scores were similar between the groups: LuPSMA was 64 (95% CI 61–67) versus 60 for cabazitaxel (95% CI 57–64). Nonetheless, the Lu177 group reported favourable outcomes compared with the cabazitaxel group in the domains fatigue (34 vs 40; P<0.05), social functioning (79 vs 73; P<0.05), insomnia (24 vs 29; P<0.05), and diarrhoea (8.3 vs 15.6; P<0.001). No domains were favourable in the chemotherapy group.

Dr Hofman concluded that these interim results support the use of LuPSMA as an alternative to cabazitaxel in men with docetaxel-treated mCRPC.

1. Hofman M. 177Lu-PSMA-617 (LuPSMA) versus cabazitaxel in metastatic castration-resistant prostate cancer (mCRPC) progressing after docetaxel: Updated results including progression-free survival (PFS) and patient-reported outcomes (PROs) (TheraP ANZUP 1603). Abstract 6, ASCO Genitourinary Cancers Symposium, 11–13 February 2021.

 

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Posted on 24 March, 202118 March, 2024