ASCO GU 2019: Results of a 50 Patient Single-Centre Phase II Prospective Trial of Lutetium-177 PSMA-617 Theranostics in mCRPC

San Francisco, CA (UroToday.com) PSMA is over-expressed in all prostate tissue, including prostatic carcinoma. Lutetium-177 (177Lu)-PSMA617 (LuPSMA) is a small radiolabeled molecule which binds to PSMA and delivers a dose of β radiation. Lutetium-177 is a good partner to help deliver the radiation because of the short range β radiation (maximal tissue penetration of <2mm), thereby decreasing the potential collateral damage to nearby organs. 

The authors of this study have previously reported on their experience of 30 men with metastatic CRPC treated in a single-center phase II prospective trial of LuPSMA.1 This abstract represents an updated analysis of an extended cohort of 50 patients.  

In this phase II trial, 50 men with PSMA-avid (defined as high PSMA expression in at least one site of metastatic disease with > 1.5 SUV of the liver) mCRPC who had progressed after standard therapies (including docetaxel and androgen-axis targeted therapies) received up to 4 cycles of LuPSMA every 6 weeks. The full protocol can be seen below: 
ResultsSchema_177LuPSMA.png

The primary endpoints were PSA response (according to PCWG2 criteria) and toxicity (according to CTCAE v4). Secondary endpoints included imaging response, PSA PFS and OS. 

75 men were screened to identify 50 patients eligible for treatment. Median PSA doubling time was 2.6 months. The majority of patients had received prior docetaxel (84%), cabazitaxel (48%), and abiraterone and/or enzalutamide (90%). Full demographic info is seen below:
PatientDemographicInfo.png

These men are heavily pretreated mCRPC patients with limited alternative options. The mean administered radioactivity was 7.5 GBq/cycle.  

In terms of response, PSA decline ≥ 50% was achieved in 32 of 50 patients (64%, 95% CI 50-77%), including 22 patients (44%, 95% CI 30-59%) with a PSA decline ≥ 80%. Best PSA response is depicted here: BestPSAResponse_ASCOGU.png

27 patients had measurable soft tissue at baseline and 56% of these patients had a partial or complete response by RECIST 1.1 criteria.  

Median PSA PFS was 6.9 months (95% CI 6.0-8.7) and median OS was 13.3 months (95% CI 10.5-18.0). Upon subsequent progression, further LuPSMA was administered to 14 patients (median 2 cycles commencing 359 days from enrolment); PSA ≥ 50% response occurred in 9 patients (64%), indicating the option for retreatment. 

The PFS KM curve:
PFS_KM_Curve.png
Patients who had a >= 50% response had a PFS of 8.3 months. 

OS K-M curve seen below:
OS_KM_Curve.png
Men who had a >= 50% PSA response had a median OS of 18 months.  

Overall, LuPSMA was well tolerated. The most common toxicities attributed to LuPSMA were transient G1-2 dry mouth in 68%, G1-2 nausea in 48%, and G1-2 fatigue in 36%. G3-4 toxicities attributed to LuPSMA were infrequent with thrombocytopenia in 10% and anemia in 10%.  

Using this expanded 50 patient cohort confirms high response rates and low toxicity with LuPSMA in men who had progressed after standard therapies. In patients who subsequently progressed and were administered further LuPSMA, high response rates were also observed, indicating that this treatment can be repeated with significant response. These results have provided the basis for randomized controlled trials currently underway – the ANZUP/PCFA TheraP trial (Lutetium-PSMA vs. cabazitaxel) and the Endocyte VISION trial.  

Presented By: Michael Hofman, FRACP, MBBS, nuclear medicine physician in the Centre for Cancer Imaging at the Peter MacCallum Cancer in Melbourne

Written by: Thenappan Chandrasekar, MD, Clinical Instructor, Thomas Jefferson University; Twitter: @tchandra_uromd, @JEFFUrology at the 2019 American Society of Clinical Oncology Genitourinary Cancers Symposium, (ASCO GU) #GU19, February 14-16, 2019 - San Francisco, CA

References: 
  1. Hofman MS, Violet J, Hicks RJ, Ferdinandus J, Thang SP, Akhurst T, Iravani A, Kong G, Ravi Kumar A, Murphy DG, Eu P, Jackson P, Scalzo M, Williams SG, Sandhu S. [177Lu]-PSMA-617 radionuclide treatment in patients with metastatic castration-resistant prostate cancer (LuPSMA trial): a single-centre, single-arm, phase 2 study. Lancet Oncol. 2018 Jun;19(6):825-833. doi: 10.1016/S1470-2045(18)30198-0. Epub 2018 May 8. 
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