Short-course (3-month) enzalutamide monotherapy in biochemically recurrent prostate cancer (BCR): Preliminary prostate specific membrane antigen tumor volume (PSMA-TV) data.
Abstract
e17109 Background: Enzalutamide (enza) monotherapy is a treatment option for BCR. Although EMBARK allowed dose interruption after 9 months of enza monotherapy, a previous study (n = 38) at the National Cancer Institute (NCI) evaluated two 3-month intermittent courses of enza without androgen deprivation (ADT). The results indicated that PSA control (disease below PSA baseline) was a median of 308 days with 3 months of enza for course 1 and 273 days for course 2, emphasizing a therapeutic approach focused on treatment free survival. No patients (pts) had progression on CT or bone scan after PSA recovery to baseline PSA after 3 months of enza for up to 2 intermittent courses. (Madan, RA et al., JITC, 2021). Although prostate specific membrane antigen (PSMA) scans are increasingly being used for response assessment in prostate cancer with presumed informative potential, it remains unknown how most therapies including enza monotherapy will impact PSMA-TV. PSMA-TV has been proposed as key PSMA readout (e.g. RECIP 1.0) but has rarely been prospectively evaluated in therapeutic trials to date. Methods: NCT06096870 is a clinical trial (n = 50) at the NCI randomizing BCR pts to either enza monotherapy or enza + PDS01ADC (IL-12 immunocytokine). Pts must have negative CT, bone scan, T > 100, and PSMA+ BCR. All pts are treated with enza for 3 months without ADT. PSMA scans are done at baseline and after 3 months of enza. Upon PSA recovery to baseline, all pts are eligible for another course of 3 months of enza if CT and bone scan remain negative. This analysis evaluates the first group of pts who had enza monotherapy only with paired PSMA before/after enza. Baseline PSMA-TV was compared with PSA response data after 3 months of enza. Results: Among the first 13 enza monotherapy pts, medians were age = 71 years, PSA = 22.5 ng/ml, PSA doubling time = 3.5 months, PSMA-TV = 11.1 milliliters. Median PSA response was -98% (-81% to -100%) for a duration of 259 days (including only 84 days of enza). The median PSMA-TV response was -71.7% (+13.2% to -100%). Of note, among 4 pts with PSA = 0 ng/ml after enza, PSMA-TV = 0 in 2 pts, PSMA-TV = -86% in a 3 rd pt but PSMA-TV = +2.8% in the 4 th pt. Furthermore, the PSMA TV increase in 4 th pt did not predict poor clinical response and that pt even had longer PSA control than a pt with a 100% PSA decline and complete response on PSMA. Conclusions: This is the first data presented evaluating PSMA-TV changes after enza in BCR without ADT. Despite this small data set, lack of concordance of PSA and PSMA responses should highlight a need to collect more data to better understand the clinical utility of PSMA scans in defining therapeutic response in BCR. It further indicates the need for caution in the use of PSMA imaging presumptively to define therapeutic benefit or lack thereof in clinical practice. Clinical trial information: NCT06096870 .
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (20)
Aanika Warner
Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD
Liza Lindenberg
National Institutes of Health, Bethesda, MD
Esther Mena
1National Cancer Institute, Lymphoid Malignancies Branch, Bethesda, United States
Jeanny B. Aragon-Ching
Inova Schar Cancer Institute, Fairfax, VA
Laura A. Sena
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University School of Medicine, Baltimore, MD
Edwin Melencio Posadas
Cedars-Sinai Medical Center, Los Angeles, CA
Helen Moon
From the Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda (A.B.A., N.S., S.N., L.L., L.C.), the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore (J.H.-C.), and the Investigational Drug Branch, Cancer Therapy Evaluation Program, National Cancer Institute, National Institutes of Health, Rockville (H.S., E.S.) — all in Maryland; the Alliance Statistics and Data Management Center, Mayo Clinic, Rochester, MN (K.V.B., M.O., C.M., G.P.B.); AdventHealth Cancer Institute and the University of Central Florida, Orlando (G.S.); Dana–Farber/Harvard Cancer Center, Boston (S.B., B.M.); UNC Lineberger Comprehensive Cancer Center, Chapel Hill (W.Y.K.), and Duke University Medical Center and Duke Cancer Institute, Durham (J.H., S.H.) — both in North Carolina; the University of Kansas Cancer Center, Westwood (R.P.); Memorial Sloan Kettering Cancer Center, New York (M.Y.T., M.J.M., J.E.R.), and Roswell Park Comprehensive Cancer Center, Buffalo (G.C.) — both in...
Marijo Bilusic
University of Miami/Sylvester Comprehensive Cancer Center, Miami, FL
Catherine Handy Marshall
Johns Hopkins University School of Medicine, Baltimore, MD
Katherine Lee-Wisdom
Megan Hausler
Genitourinary Malignancies Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD
Monique Williams
Genitourinary Malignancies Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD
Amy Hankin
Genitourinary Malignancies Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD
Deborah Jolissaint
Walter Reed National Military Medical Center, Bethesda, MD
Gregory T. Chesnut
The Center for Prostate Disease Research/Walter Reed, Bethesda, MD
William Douglas Figg
Fatima Karzai
Peter L. Choyke
Ravi Amrit Madan
Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD
Melissa Lauren Abel
Genitourinary Malignancies Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD