Fluciclovine PET imaging is the most sensitive imaging modality we have to date that is United States Food and Drug Administration (FDA) approved and available for widespread use. Fluciclovine is a synthetic amino acid that is uptaken by amino acid transporters that are upregulated in many cancer cells, including prostate cancer. A key advantage of fluciclovine is that it has low renal excretion, which is ideal for imaging the pelvis. The sensitivity and specificity of PET imaging with fluciclovine are superior to choline in a direct comparative trial of patients in the biochemically recurrent prostate cancer disease state.1 The FDA approval is in men with suspected prostate cancer recurrence based on elevated prostate-specific antigen (PSA) levels following prior treatment.2
Recently, fluciclovine PET imaging has shown a greater impact by demonstrating that key treatment decisions can be altered based on imaging findings. Specifically, the FALCON trial, performed in the United Kingdom, identified 64% of men to undergo a post-fluciclovine PET/CT scan management change.3 A similarly designed, but larger, multicenter trial in the United States termed LOCATE found 59% of patients to have a change in management after fluciclovine PET/CT imaging.4 Although encouraging, it is yet to be proven that patient outcomes, in the case of efficacy, toxicity, or quality of life, are improved by these imaging-driven alterations in management.
Almost a year and a half ago, I summarized ongoing clinical trials using fluciclovine PET imaging.5 Many of the clinical trials that were highlighted before were focused on improved staging and detection. However, the landscape has changed and there are many new clinical trials available focused on the next logical set of questions. For instance, rather than just identifying prostate cancer sites, there is a now greater emphasis on metastasis directed therapy and treatment response.
With metastasis directed therapy, the randomized Phase III ECOG/ACRIN trial below (NCT04423211) has significant potential to change the future standard of care, as fluciclovine PET/CT imaging could guide salvage radiation therapy and even direct oligometastatic directed therapy. Additionally, this trial inquires whether systemic treatment intensification may offer benefit. One interesting feature is that this trial has the potential to add in other next-generation PET imaging modalities, e.g. prostate-specific membrane antigen (PSMA) PET, to direct therapy, as these other technologies have promise to gain regulatory approval during the accrual lifespan of this trial. Another single institutional trial looks to address a truly unmet need. The Flu-BLAST-PC trial (NCT04175431) will only enroll patients who have previously received radical prostatectomy and either adjuvant or salvage radiation. This population has no additional local therapy options left, and therefore, may identify oligometastatic lesions amenable to laparoscopic lymph node dissection or radiation therapy to try to improve outcomes by incorporating a local therapy combined with systemic androgen deprivation therapy with abiraterone acetate.
Treatment response trials utilizing next-generation PET imaging will be incredibly important in the future. This acknowledges that eventually, PET/CT imaging could be standard for all prostate cancer disease states. Hence, eventually, identification of disease to guide management and direct surgery and radiation efforts will likely extend to the use of PET imaging for treatment and pharmacodynamic response. Recognizing that, our field needs to start to understand what to expect in response to both successful and unsuccessful systemic therapeutic outcomes for individual patients and start to define these responses or lack thereof by PET. Identifying baseline and early response PET changes may lead to improved patient outcomes and offer useful prognostic and even potentially predictive information. As a result, the two clinical trials below seek to determine fluciclovine PET changes in response to abiraterone acetate both in the metastatic castration-resistant (NCT04158245) and castration-sensitive (NCT04134208) disease states.
As the field of next-generation PET imaging evolves, we recognize that there is an increasing amount of data emerging with PSMA-targeted PET imaging, and it would not be surprising to see PSMA PET imaging become the standard of care in the not too distant future. However, at this point in time, we do not yet have regulatory approval in the United States for PSMA PET imaging. Hence, we must focus on optimizing our utilization of fluciclovine PET imaging. That will only come with aggressive efforts to accrue to clinical trials that incorporate fluciclovine PET imaging with clinical endpoints that inform impactful clinical outcomes. Below, we have outlined multiple ongoing trials with fluciclovine PET, occurring in various disease states, with a strong emphasis on those trials with metastasis-directed therapy and treatment response components.
Clinical trials with 18F-fluciclovine PET/CT imaging for biochemical recurrence and metastasis-directed therapy:
- Randomized, Phase III ECOG/ACRIN trial to direct salvage radiation and also +/- apalutamide (NCT04423211)
- Flu-BLAST-PC post radical prostatectomy and adjuvant/salvage radiation and also incorporating abiraterone acetate plus prednisone (NCT04175431)
- To direct radiotherapy and radium-223 to bone metastases (NCT03707184)
Clinical trials with 18F-fluciclovine PET/CT Imaging for metastatic prostate cancer treatment response:
- Metastatic castration-resistant prostate cancer treatment response to abiraterone acetate (NCT04158245)
- Metastatic castration-sensitive prostate cancer treatment response to androgen deprivation therapy and abiraterone acetate (NCT04134208)
Clinical trials with 18F-fluciclovine PET/CT imaging for detection of recurrence:
- Detection of biochemical recurrence compared to standard of care imaging (NCT04234399)
- Detection of recurrence with fluciclovine PET/MRI after prior cryoablation (NCT04009083)
- Detection of recurrence to guide salvage radiation or androgen deprivation therapy (NCT03996993)
- Comparing biochemical recurrence detection between fluciclovine vs. standard imaging +/- sodium fluoride PET imaging (NCT03527199)
- Bone metastatic biopsies to confirm fluciclovine PET findings (NCT03496844)
Clinical trials with 18F-fluciclovine PET/CT imaging for initial prostate cancer identification:
- 18F-fluciclovine PET/MRI to identify potential previously false negative MRI findings (NCT03635866)
Written by: Evan Yu, MD, Professor, Department of Medicine, Division of Oncology, University of Washington School of Medicine, Member, Clinical Research Division, Fred Hutchinson Cancer Research Center, Clinical Research Director, Genitourinary Oncology, Seattle Cancer Care Alliance, Medical Director, Clinical Research Service, Fred Hutchinson Cancer Research Consortium
1. Nanni, Cristina, Lucia Zanoni, Cristian Pultrone, et al. "18 F-FACBC (anti1-amino-3-18 F-fluorocyclobutane-1-carboxylic acid) versus 11 C-choline PET/CT in prostate cancer relapse: results of a prospective trial." European journal of nuclear medicine and molecular imaging 43, no. 9 (2016): 1601-1610.
2. Axumin® (fluciclovine F18) Injection (Prescribing Information). Blue Earth Diagnostics, Ltd. August 2016.
3. Scarsbrook A., Bottomley D., Teoh E., et al. Effect of 18F-Fluciclovine Positron Emission Tomography on the Management of Patients With Recurrence of Prostate Cancer: Results From the FALCON Trial. Int J Radiat Oncol Biol Phys 2020; 107(2):316-324.
4. Andriole, Gerald L., Lale Kostakoglu, Albert Chau, Fenghai Duan, Umar Mahmood, David A. Mankoff, David M. Schuster, and Barry A. Siegel. "The impact of positron emission tomography with 18F-fluciclovine on the treatment of biochemical recurrence of prostate cancer: results from the LOCATE trial." The Journal of urology 201, no. 2 (2019): 322-331.
5. Yu, Evan. “Fluciclovine (Axumin®) PET/CT Imaging in Prostate Cancer: More Uses than Just for Recurrent Disease?” Accessed August 24, 2020. https://www.urotoday.com/clinical-trials/from-the-editor/110885-from-the-desk-of-evan-yu-fluciclovine-axumin-pet-ct-imaging-in-prostate-cancer-more-uses-than-just-for-recurrent-disease.html.
Cristina Nanni on Flucicovine F18 (FACBC) in Prostate Cancer - State of the Art Presentation