The inclusion of 18F- fluciclovine PET/CT to guide post-prostatectomy salvage radiotherapy improved outcomes, researchers reported.
Results from the EMPIRE-1 trial showed that when the radiotracer was used to guide final radiotherapy treatment decisions, patients had an approximately 12% absolute improvement in event-free survival (EFS) at 3 years compared with patients who underwent therapy guided by conventional imaging, according to Ashesh Jani, MD, of Winship Cancer Institute of Emory University in Atlanta, and colleagues.
In addition, as shown in their study online in The Lancet, toxicity was similar in both groups.
Jani told MedPage Today that the trial, which began in 2012, was born out of a desire to improve outcomes in post-prostatectomy patients. “We recognized there was great potential here with this imaging test to improve radiation decisions, to improve radiation planning, and even exclude patients who may not benefit from radiation,” he said. “We saw it as a valuable test.”
Co-author David Schuster, MD, director of Winship’s Division of Nuclear Medicine and Molecular Imaging, explained that like most new imaging tests, 18F-fluciclovine PET allows physicians to see smaller and subtler cancers, which results in changes in management: “But the question is, does it actually change outcomes?”
The team’s single-center, open-label, phase II/III randomized controlled trial, conducted from Sept. 2012 to March 2019, included 165 patients who had undergone radical prostatectomy with biochemical recurrence or persistence, and were evaluated with conventional imaging. Patients were assigned on a 1:1 basis to receive radiotherapy guided by either conventional imaging, or conventional imaging plus 18F-fluciclovine PET/CT, and followed for a median of 3.52 years.
The primary endpoint was 3-year EFS, with events defined as biochemical or clinical recurrence or progression, or initiation of systemic therapy, using univariate and multivariable analyses in patients who received radiotherapy.
Three-year EFS was 63.0% (95% CI 49.2-74.0; 22 events) in the conventional imaging group compared with 75.5% (95% CI 62.5-84.6; 15 events) in the 18F-fluciclovine PET/CT group (a difference of 12.5 percentage points; 95% CI 4.3-20.8).
A multivariable analysis for EFS showed a significantly higher risk of events in the conventional imaging group (HR 2.04, 95% CI 1.06-3.93).
Toxicity was similar in the two groups, with the most common adverse events late urinary frequency or urgency (46% of patients in the conventional imaging group; 41% in the fluciclovine group), and acute diarrhea (14% in the conventional imaging group; 21% in the fluciclovine group), the researchers reported. Grade 3 toxic effects were infrequent in both groups, and none of the patients had grade 4 or 5 adverse events.
Asked for his perspective, Thomas Hope, MD, director of molecular therapy at the University of California San Francisco, who was not involved with the study, said: “It is an academic feat to have a single academic center randomize patients to demonstrate that there is a benefit to targeting lesions seen in molecular imaging, compared to conventional imaging, So in that sense it is very powerful.”
He noted, however, that the trial began in an area before the use of prostate-specific membrane antigen (PSMA)/PET. “So the question is how is the data from EMPIRE-1 relevant in a PSMA/PET era? Presumably PSMA/PET will be even better, because we all know it has a higher sensitivity and specificity,” he told MedPage Today. “I think this study is still relevant, though. If you target these things we see with molecular imaging, patients really do better, and that does support the use of these radiotracers.”
Schuster said EMPIRE-1 has “set a certain bar: We have a proof-of-concept of how molecular imaging can not only actually improve our ability to find cancer, but also improve outcomes.”
Jani and Schuster noted that they are also leading another trial – EMPIRE-2 – which is similar to EMPIRE-1 in that it has EFS as the primary endpoint, but will extend randomly assign patients to either PSMA or 18F-fluciclovine PET/CT.
“The reason we are doing EMPIRE-2, which is over half accrued, is that it is not necessarily a foregone conclusion that one will improve outcomes greater than the other, because there may be a better detection ability in certain areas,” Schuster explained. “For example, we believe fluciclovine has a better ability to detect local disease because of the little-to-no bladder activity, while PSMA may have some advantages in disease outside the pelvis. And PSMA is a receptor tracer, while fluciclovine works on metabolism.”
But, as for which one will be better at improving outcomes, Schuster said: “The only way to look at that is with a randomized controlled trial, such as we did with EMPIRE-1.”
Study limitations, the researchers said, included that there was some variability in pre-PET decisions, particularly related to general target volumes, although post-PET decisions were “rigidly followed per protocol”; and that the role of androgen-deprivation therapy is difficult to interpret in the study and was not formally analyzed. In addition, the study is from a single center, although it was done at multiple sites and involved multiple treating radiation oncologists, and although median follow-up was long enough to report the primary study endpoint, confirmation of EFS with longer follow-up is still warranted.
The study was funded by the NIH, Blue Earth Diagnostics (fluciclovine synthesis cassettes to Emory University), and the Biostatistics Shared Resource of Winship Cancer Institute of Emory University.
Jani reported a financial relationship with Blue Earth Diagnostics. Schuster reported participating through the Emory University Office of Sponsored Projects in sponsored grants including those funded or partially funded by Blue Earth Diagnostics, Nihon Medi-Physics, Telix Pharmaceuticals, Advanced Accelerator Applications, FUJIFILM Pharmaceuticals, and Amgen; and also reported financial relationships with Syncona, AIM Specialty Health, Global Medical Solutions Taiwan, and Progenics Pharmaceuticals.
Hope also reported a financial relationship with Blue Earth Diagnostics.