TheraP: A randomised phase II trial of ¹⁷⁷Lu-PSMA-617 (LuPSMA) theranostic versus cabazitaxel in metastatic castration resistant prostate cancer (mCRPC) progressing after docetaxel: Initial results (ANZUP protocol 1603).

Abstract

5500 Background: LuPSMA is a radiolabeled small molecule that delivers therapeutic β-radiation to PSMA-expressing tumors. Encouraging efficacy and safety has been shown in non-randomized studies of mCRPC. TheraP is a randomized phase II trial comparing LuPSMA vs cabazitaxel in men with mCRPC progressing after docetaxel. Methods: Men with mCRPC, and imaging with 68Ga-PSMA-11 and 18F-FDG PET/CT that confirmed high PSMA-expression and no sites of FDG-positive/PSMA-negative disease, were randomly assigned (1:1) to LuPSMA (6-8GBq q6weeks up to 6 cycles) vs cabazitaxel (20mg/m2 q3weeks up to 10 cycles); stratified by disease burden (>20 vs ≤20 sites), prior novel antiandrogens (NAA; abiraterone or enzalutamide), and study site. The primary endpoint was PSA response rate (PSA50-RR) defined by ≥50% reduction. Secondary efficacy endpoints included PSA-progression-free survival (PSA-PFS) and overall survival (OS). Data cut-off was 31DEC19 at this first pre-specified analysis. Results: 200 (median age 72 y, prior NAA 91%, >20 lesions 78%) of 291 PET screened men were randomised to LuPSMA (N=99) or cabazitaxel (N=101). 17 patients withdrew or died before receiving study treatment (1 LuPSMA vs 16 cabazitaxel). The PSA50-RR was higher in those assigned LuPSMA than cabazitaxel (65/99 [66%; 95%CI 56-75] vs 37/101 [37%; 95%CI 27-46]; P<0.001). At a median follow-up of 11.3 months, LuPSMA significantly improved PSA-PFS (HR 0.63, 95%CI 0.45-0.88, P=0.007; 143 events with next pre-specified analysis planned after 170 events). Efficacy results were similar when analyses were restricted to per-protocol treated men. OS data remains immature (57 deaths). Grade III-IV adverse events (AEs) occurred in 31/98 (32%) LuPSMA-treated men vs 42/85 (49%) in cabazitaxel-treated men. Discontinuations for toxicity occurred in 1/98 (1%) LuPSMA vs 3/85 (4%) cabazitaxel-treated. There were no treatment-related deaths. Conclusions: In men with docetaxel-treated mCRPC, LuPSMA was more active (PSA50-RR) than cabazitaxel with relatively fewer G3-4 AEs and PSA-PFS favoring LuPSMA. Clinical trial information: NCT03392428 .

Meeting report from the Prostate Cancer Foundation PSMA theranostics state of the science meeting

“…If this trial is successful this will likely became the de‐facto standard. The TheraP trial 88 uses an identical schedule, but with a declining amount of administered radioactivity, commencing at 8.5 GBq and decreasing by 0.5 GBq per cycle to 6 GBq for cycle 6. The total administered radioactivity across six cycles is very similar with these two regimens.…”

“…A single site study at Johns Hopkins University in patients with biochemically recurrent prostate cancer reported sensitivity for 18 F-DCFPyL ranging from 59.1% at PSA levels between 0.20 and 1.00 ng/mL (N = 22) to 88.9% in patients with PSA more than 1.00 ng/mL (N = 9). In a study at the NCI, the sensitivity of 18 F-DCFPyL in 90 patients with BCR was 47.6% in patients with PSA 0.20 to 0.5 ng/mL, 50.0% in patients with PSA 0.5 to 1.0 ng/mL, 88.9% in patients with PSA 1.0 to 2.0 ng/mL, and 94.0% in patients with PSA more than 2.0 ng/mL. 31 On a per-patient basis, the positive predictive value in this study was 93.3% by histopathologic validation and 96.2% by histology, imaging and/or, clinical follow-up.…”

Genitourinary cancers—best of ASCO 2020

“…Concerning side effects, the most Genitourinary cancers-best of ASCO 2020 K short review Table 3 Updated outcome and descriptive parameters of the three phase 3 trials evaluating efficacy of enzalutamide [17], darolutamide [18] and apalutamide [19] versus placebo in the treatment of nonmetastatic castration-resistant prostate cancer common from LuPSMA were dry eyes, dry mouth and thrombocytopenia. The most common grade 3 or 4 toxicity was thrombocytopenia (11%) [20].…”

Lutetium-177-PSMA-I&T as metastases directed therapy in oligometastatic hormone sensitive prostate cancer, a randomized controlled trial

“…To date, only one prospective trial of 177 Lu-PSMA-617 has been published, showing efficacy in 57% of end-stage PC patients and 177 Lu-PSMA was generally well tolerated [20]. These observations were recently confirmed at ASCO, with the presentation of the initial results of the TheraP trial comparing 177 Lu-PSMA-617 to cabazitaxel in mCRPC patients (NCT03392428) [26]. The pivotal trial of 177 Lu-PSMA-617 in end-stage PC, called the VISION study (clinicaltrial.gov identifier: NCT03511664), is currently being finalized.…”

“…177 Lu is a beta (β − ) radiation emitter with a maximum energy of 0.50 MeV with maximum penetration depth of 2 mm and a 6.7-days half-life. 177 Lu labelled PSMA is a promising new therapeutic approach and frequently used in compassionate use programs worldwide [22][23][24][25][26]. To date, only one prospective trial of 177 Lu-PSMA-617 has been published, showing efficacy in 57% of end-stage PC patients and 177 Lu-PSMA was generally well tolerated [20].…”