Radiographic Progression With and Without Prostate-Specific Antigen Rise in Patients With Advanced Prostate Cancer Treated With Enzalutamide

Author(s): Andrew J. Armstrong, MD, ScM, FACP¹; Arun A. Azad, MBBS, PhD^2,3; Taro Iguchi, MD, PhD⁴; Arnulf Stenzl, MD⁵; Nicolas Mottet, MD, PhD⁶; David Russell, MD⁷; Matt Rosales, PhD⁸; Gabriel P. Haas, MD⁹; Fred Saad, MD¹⁰; Maha Hussain, MD, FACP, FASCO¹¹; Cora N. Sternberg, MD, FACP¹²;

Source: DOI: 10.1200/JCO-24-02829

Dr. Anjan Patel's Thoughts

An important post-hoc analysis from ARCHES and PROSPER that quantifies something we've suspected clinically, roughly 1 in 4 enzalutamide-treated patients who progress radiographically have no prostate-specific antigen (PSA) rise, and the majority won't meet PCWG2/3 PSA progression criteria. Liver metastases were 5-fold more common at radiographic progression on enzalutamide versus control, suggesting lineage plasticity and AR-independent clones are the culprit. Bottom line for practice: don't wait for PSA to rise before imaging your metastatic hormone-sensitive prostate cancer (mHSPC) and nonmetastatic castration-resistant prostate cancer (nmCRPC) patients on ARPIs, periodic cross-sectional imaging, especially in the first two years, is warranted regardless of PSA trend.

PURPOSE

In patients who received enzalutamide, we characterized the development of radiographic progression (rPD) without prostate-specific antigen (PSA) rise or progression in metastatic hormone-sensitive prostate cancer (mHSPC) and nonmetastatic castration-resistant prostate cancer (nmCRPC).

METHODS

We conducted a post hoc analysis in two phase III trials (N = 2,551; ARCHES [ClinicalTrials.gov identifier: NCT02677896]; PROSPER [ClinicalTrials.gov identifier: NCT02003924]) for co-occurrence of rPD ± Prostate Cancer Working Group 2/3-defined PSA progression, and rPD ± any PSA rise from baseline/nadir by treatment. Kaplan-Meier methods were used for overall survival (OS) outcomes.

RESULTS

In ARCHES, 3.5% and 8.5% of 574 patients with mHSPC treated with enzalutamide plus androgen-deprivation therapy (ADT) had no PSA rise or PSA progression rPD, respectively. Of 79 patients with rPD who received enzalutamide plus ADT, 25.3% had no PSA rise and 62.0% did not meet PSA progression criteria compared with 7.4% and 38.3% of 188 patients with rPD treated with ADT alone, respectively. In PROSPER, 4.4% and 10.3% of 933 patients with nmCRPC treated with enzalutamide plus ADT had no PSA rise or PSA progression, respectively, rPD. However, of 187 patients with rPD who received enzalutamide plus ADT, 21.9% had no PSA rise and 51.3% did not meet PSA progression criteria compared with 3.6% and 18.8% of 224 patients treated with placebo/ADT, respectively. Liver metastases were >5-fold higher in enzalutamide-treated patients with rPD events versus control, although sample size was small. Compared with no rPD, enzalutamide-treated patients with rPD ± PSA rise or progression had worse OS.

CONCLUSION

Given the frequent discordance and poor prognosis of imaging-based progression in the absence of PSA changes during enzalutamide treatment in mHSPC and nmCRPC, periodic surveillance using imaging is recommended.

Author Affiliations

¹Department of Medicine, Division of Medical Oncology, Duke Cancer Institute Center for Prostate and Urologic Cancer, Duke University, Durham, NC; ²Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia; ³Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Australia; ⁴Department of Urology, Kanazawa Medical University, Ishikawa, Japan; ⁵Department of Urology, University of Tübingen, Tübingen, Germany; ⁶Department of Urology, University Hospital, St Etienne, France; ⁷Pfizer Inc, New York, NY; ⁸Astellas Pharma Global Development, Northbrook, IL; ⁹Global Product Development, Astellas Pharma Inc, Northbrook, IL; ¹⁰University of Montreal Hospital Center, Montreal, QC, Canada; ¹¹Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL; ¹²Englander Institute for Precision Medicine, Meyer Cancer Center, Weill Cornell Medicine, New York, NY

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