ASCO GU 2021: 177Lu-PSMA-617 Versus Cabazitaxel in Metastatic Castration-Resistant Prostate Cancer Progressing After Docetaxel: Updated Results Including Progression-Free Survival and Patient-Reported Outcomes (TheraP ANZUP 1603)

(UroToday.com) Targeting the PSMA protein is one of the most promising emerging approaches to treating advanced prostate cancer.  PSMA, the Prostate Specific Membrane Antigen, is expressed predominantly on prostate cells, as well as to a lesser degree in proximal tubules of the kidney, the small intestine, and oromaxillary glands.  As expression is further increased with prostate carcinogenesis, targeting of PSMA has been increasingly enticing.  Several approaches including small molecule- and antibody-based technologies1,2 have emerged carrying a “payload” of chemo- or radiotherapy or engineered to bring immune effector cells in close proximity to prostate cancer cells.  Last year, the authors (Dr. Hofman et al.) presented the results of the randomized phase II study, TheraP, which compared 177Lu-PSMA-617 to cabazitaxel in the treatment of post-docetaxel metastatic castration resistant prostate cancer (mCRPC).1  There, the small molecule 617 was conjugated to a beta-emitting radionuclide (177Lu) and they reported improved activity (via PSA50), improved PSA-PFS, and fewer Grade 3 or 4 adverse events, as compared to cabazitaxel therapy.



Dr. Michael Hofman and colleagues presented updated data from the TheraP study, including patient-reported outcomes (PROs) having now met pre-specified event targets.  Among 200 men with mCRPC enrolled (median age 72 years, 91% with prior enzalutamide and/or abiraterone acetate), all were confirmed to have evidence of high PSMA expression via 68Ga-PSMA-11 imaging.  They were randomly assigned to q6w cycles of 6-8.5 GBq of LuPSMA (n = 99, up to 6 cycles) or cabazitaxel (20 mg/m2, q3w, n =101, up to 10 cycles).  At a median follow up of 18.4 months, PFS (via PCWG3) was significantly longer in the LuPSMA-treated patients (at 1 year, 19% [95% CI 12-27%] versus 3% [95% CI 1-9%]; HR 0.63 [95% CI 0.46-0.86], p = 0.003).  Hazard ratios for radiographic PFS (rPFS) and PSA-PFS were similar.  Overall response rate (ORR) was doubled in LuPSMA-treated patients (n = 78, 49% v 24%, RR 2.1, 95%CI 1.1-4.1, p = 0.019). 

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Among PROs, pain responses were observed in 60% LuPSMA-treated patients versus 43% of cabazitaxel-treated patients, among 90 evaluable subjects (RR 1.42, 95% CI 0.84-4.48, p = 0.10).  Other PROs were relatively similar and rates of Grade 3/4 continue to favor LuPSMA treatment.

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Although overall survival (OS) data remain immature, these updates from TheraP ANZUP1603 continue to indicate activity in and efficacy and safety relative to cabazitaxel in men who have progressive mCRPC after docetaxel treatment.  As highlighted by Dr. Hofman, the strengths of these data include an active treatment comparison arm (i.e. cabazitaxel) and a weakness of high rates of withdrawal in that arm. The PSMA-targeting approach within this study as well as alternative, potentially complementary approaches (e.g. antibody-targeting, alpha-emitting) in simultaneous trials continue to add support for the bright future of PSMA-targeted radiotherapies in prostate cancer.

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Presented by: Michael S. Hofman, MBBS (Hons), FRACP, FAANMS, FICIS, ANZUP Cancer Trials Group; Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.

Written by: Jones Nauseef MD, PhD. Fellow, Division of Hematology and Oncology, Weill Cornell Medicine/New York Presbyterian Hospital. Twitter: @DrJonesNauseef during the 2021 ASCO Genitourinary Cancers Symposium (ASCO GU), February 11th to 13th, 2021

References:

  1. Hofman MS, Emmett L, Sandhu SK, Aravani A, Joshua AM, Goh JC, Pattison DA, Tan TH, Kirkwood ID, Ng S, Francis RJ, Gedye C, Rutherford NK, Zhang AY, McJannett MM, Stockler MR, Violet JA, Williams S, Martin AJ, Davis ID. TheraP: A randomized 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). J Clin Oncol 28: 2020 (suppl, abtra 5500). 10.1200/JCO.2020.38.15_suppl.5500
  2. Tagawa ST, Milowsky MI, Morris M, Vallabhajosula S, Christos P, Akhtar NH, Osborne J, Goldsmith SJ, Larson S, Tasker NP, Scher HI, Bander NH, Nanus DM.  Phase II study of Lutetium-177-labeled anti-prostate-specific membrane antigen monoclonal antibody J591 for metastatic castration-resistant prostate cancer. Clin Cancer Res, 2013. 19(18): p. 5182-91.
Related Content:

ANZUP Reports A New Class of Effective Therapy for Men with Metastatic Castration-Resistant Prostate Cancer

[¹⁷⁷Lu]Lu-PSMA-617 Versus Cabazitaxel in Patients with Metastatic Castration-Resistant Prostate Cancer (TheraP): A Randomised, Open-Label, Phase 2 Trial
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