ASCO 2019: Prospective Head-To-Head Comparative Phase 3 Study Between 18F-Fluciclovine and 68Ga-PSMA-11 PET/CT in Patients with Early Biochemical Recurrence of Prostate Cancer

Chicago, IL ( Two PET/CT imaging tests for detection and localization of prostate cancer tumor sites in patients with biochemical recurrence have been introduced recently: 18F-fluciclovine PET/CT targeting the upregulated amino acid transporter activity, and PSMA PET/CT targeting the overexpression of the transmembrane prostate-specific membrane antigen via its extracellular molecule. It is unknown which test performs better, especially in patients with biochemical recurrence at low PSA levels (<2.0 ng/mL).  Jeremie Calais and colleagues presented results of a prospective single-center, single-arm, blinded, head-to-head phase 3 study of paired 18F-fluciclovine and 68Ga-PSMA-11 PET/CT scans for localizing early biochemical recurrence of prostate cancer after radical prostatectomy. 

This study had 50 consecutive patients with biochemical recurrence and PSA levels ranging from ≥0.2 to ≤2.0 ng/mL without any prior salvage therapy. All patients underwent 18F-fluciclovine and 68Ga-PSMA-11 PET/CT scans within ≤15 days. PET/CT scans were each interpreted by three independent blinded expert readers not involved in the study design and data acquisition. Region consensus interpretation (T, N, M1a, M1b, and M1c) was generated based on majority rule in cases of reader disagreement (2 vs 1). PET/CT scans were considered as positive if any region was rated as positive. Detection rates per-patient and per-region served as the primary study endpoint. Secondary endpoints included detection rates stratified by PSA, sensitivity and PPV verified by histopathology, clinical imaging and follow-up, and inter-reader agreement.

The median age of patients was 68 years (IQR 64-74), and 22% of patients were N1. The median of the last PSA before PET/CT was 0.48 ng/mL (IQR 0.38-0.83) The median time interval between the 2 scans was 6 days (range 1-15). The detection rates were significantly lower with 18F-fluciclovine PET/CT than with 68Ga-PSMA-11 PET/CT per-patient (26% vs 56%; p = 0.003) and per-region for pelvic nodes (N) (8% vs 30%; p = 0.003) or any extra-pelvic lesions (M) (0% vs 16%; p = 0.008):

Reader agreement for 68Ga-PSMA-11 PET/CT image interpretations was significantly higher than for 18F-fluciclovine PET/CT (0.67 vs 0.20; p = 0.002). In patients with PSA levels from 0.2-0.5 ng/mL, 0.5-1.0 ng/mL, and 1.0-2.0 ng/mL, detection rates were 7/26 (27%), 5/18 (28%), and 1/6 (17%) with 18F-fluciclovine PET/CT, and 12/26 (46%), 12/18 (67%), and 4/6 (67%) with 68Ga-PSMA-11 PET/CT, respectively. Per patient sensitivity was 33% (95%CI 15-58%) and 66% (95%CI 42-85%) for 18F-fluciclovine PET/CT and 68Ga-PSMA-11 PET/CT, respectively (OR 3.5, 95% CI 0.67-34.5).

This study concluded with several take-home messages:
  • Due to higher lesion-to-background ratio, 68Ga-PSMA-11 PET/CT demonstrates superior detection rates and reader agreement than 18F-fluciclovine PET/CT
  • The primary and secondary endpoints were met: 68Ga-PSMA-11 PET/CT detection rates per patients, for pelvic lymph node regions, and for extra-pelvic metastasis were more than twice as high for those for 18F-fluciclovine PET/CT
  • PSMA should be the PET agent of choice when PET/CT imaging is considered for subsequent treatment management decisions in patients with prostate cancer and post-radical prostatectomy biochemical recurrence at low PSA levels and should become the standard of care in these patients
  • Whether early detection of biochemical recurrence sites by PET/CT imaging affects patient outcomes is the subject of ongoing phase 3 trials
Clinical trial information: NCT03515577

Presented by: Jeremie Calais, MD, MSc, UCLA Nuclear Medicine Department, Los Angeles, CA

Co-Authors: Francesco Ceci, Matthias Eiber, Tore Bach-Gansmo, Cristina Nanni, Bital Savir-Baruch, Michael Hofman, Tom Hope, Christoph Rischpler, David Elashoff, Tristan Grogan, Magnus Dahlbom, Roger Slavik, Jeannine Gartmann, Robert Evan Reiter, Matthew Rettig, Hossein Jadvar, Wolfgang P Fendler, Johannes Czernin; UCLA, Los Angeles, CA; University of Turin, Turin, Italy; Rechts der Isar University Hospital, Technical University of Munich, Munich, Germany; Oslo University Hospital, Oslo, Norway; Bologna University School of Medicine, Bologna, Italy; Loyola University Medical Center, Maywood, IL; Peter MacCallum Cancer Centre, Melbourne, Australia; UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA; University of Essen, Essen, Germany; University of California Los Angeles, Los Angeles, CA; Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, CA; Institute of Urologic Oncology, University of California, Los Angeles, Los Angeles, CA; UCLA Jonsson Comprehensive Cancer Center, Los Angeles, CA; University of Southern California, Los Angeles, CA

Written by: Zachary Klaassen, MD, MSc, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia @zklaassen_md at the 2019 ASCO Annual Meeting #ASCO19, May 31-June 4, 2019, Chicago, IL USA