Data from the phase 3 SPOTLIGHT trial indicated that 18F-rhPSMA-7.3 PET yielded a positive detection rate in patients with recurrent prostate cancer, and increased along with prostate-specific antigen level.
18F-rhPSMA-7.3 PET, a radiohybrid prostate-specific membrane antigen (PSMA)–PET imaging agent, yielded a robust detection rate in a population of patients diagnosed with recurrent prostate cancer who had an array of different baseline characteristics, according to data from the phase 3 SPOTLIGHT study (NCT04186845) that were presented during the 2022 American Society for Radiation Oncology (ASTRO) Annual Meeting.1,2
Among all patients in the trial’s efficacy evaluable population, 18F-rhPSMA-7.3 detection rates were high across all blinded central readers, with a patient-level detection rate of over 80% by majority read. The analysis presented at ASTRO drilled down on these data and examined the impact of baseline PSA level, PSA doubling time (PSADT), Gleason score, and prior therapy on 18F-rhPSMA-7.3 detection rates.
When sharing the results at the meeting, lead author Benjamin Lowentritt, MD, Chesapeake Urology Research Associates, Towson, Maryland, said, “While detection rates generally increased with increasing baseline PSA levels, they remained uniformly high over a wide range of PSADT and Gleason scores. These data support the clinical utility of 18F-rhPSMA-7.3 PET for a broad range of patients with recurrent prostate cancer.”
The multicenter, single-arm SPOTLIGHT trial enrolled male patients who were at least 18 years of age and received prior curative intent treatment for localized prostate cancer. Patients were required to have elevated PSA levels that could indicate biochemical recurrence and be eligible for salvage therapy.
18F-rhPSMA-7.3 was administered at a dose of 296 MBq (8 mCi) and PET/CT scans were given between 50 and 70 minutes following injection. Scans were then evaluated by 3 blinded central readers. The Standard of Truth was histopathology or confirmatory conventional imaging. Biopsies took place with 60 days following PET scans, and confirmatory imaging was conducted within 90 days.
The overall efficacy population included 389 patients, with a median PSA of 1.10 ng/mL (range, 0.03-1.35). Among these individuals, the patient-level 18F-rhPSMA-7.3 detection rate by majority read was 83%.
Lowentritt et al further assessed this detection rate based on PSA level and determined that at the patient level, detection rates were 64%, 76%, 93%, 98%, 94%, and 100%, for patients with baseline PSA levels of <0.5 ng/mL (n = 121), 0.5 to <1.0 ng/mL (n = 67), 1.0 to <2.0 ng/mL (n = 45), 2.0 to <5.0 ng/mL (n = 88), 5.0 to <10.0 ng/mL (n = 36), and ≥10.0 ng/mL (n = 32), respectively.
“There is a good detection rate even [with PSA levels] starting as low as 0.5 ng/mL, and certainly the detection rate went up along with the PSA level,” said Lowentritt.
Analysis of detection rates by PSA at the regional level found that the detection rates in the prostate/bed were 22%, 28%, 31%, 52%, 50%, and 69% for the <0.5 ng/mL, 0.5 to <1.0 ng/mL, 1.0 to <2.0 ng/mL, 2.0 to <5.0 ng/mL, 5.0 to <10.0 ng/mL, and ≥10.0 ng/mL groups, respectively.
The detection rates in the pelvic lymph nodes were 18%, 37%, 38%, 34%, 36%, and 31% for the
for the <0.5 ng/mL, 0.5 to <1.0 ng/mL, 1.0 to <2.0 ng/mL, 2.0 to <5.0 ng/mL, 5.0 to <10.0 ng/mL, and ≥10.0 ng/mL groups, respectively. And the detection rates in the extrapelvic sites were 21%, 39%, 60%, 44%, 50%, and 66%, for the <0.5 ng/mL, 0.5 to <1.0 ng/mL, 1.0 to <2.0 ng/mL, 2.0 to <5.0 ng/mL, 5.0 to <10.0 ng/mL, and ≥10.0 ng/mL groups, respectively.
When examining detection rates by PSA at the regional level, “You see that as the PSA level goes up, [the detection rates] in the extrapelvic sites certainly increase, whereas the pelvic lymph nodes kind of level off after a PSA of about 0.5 to 1.0 ng/mL,” explained Lowentritt.
Lowentritt said PSADT data were available for 143 patients and Gleason scores were available for 367 patients.
Assessment by prior therapy showed that among patients with prior prostatectomy and PSADTs of <6, ≥6 to <12, ≥12 to <24, and ≥24 months, the detection rates were 78%, 70%, 77%, and 83%, respectively. In patients with Gleason scores of ≤6, 7, 8, 9, and 10, the detection rates were 89%, 76%, 86%, 83%, and 100%, respectively. In the prior radiation therapy cohort, the detection rates were 100% across all PSADT and Gleason score subgroups.
“Detection rates were uniformly high across all PSADT and baseline Gleason scores for patients who underwent prostatectomy or who had radiation therapy,” said Lowentritt.
Regarding safety, there were no serious adverse events (AEs) considered to be related to 18F-rhPSMA-7.3 PET. Among all 389 patients, 16 (4.1%) experienced at least 1 treatment-emergent AE potentially related to 18F-rhPSMA-7.3. The most common AEs were hypertension (1.8%), diarrhea (1.0%), injection site reaction (0.5%), and headache (0.5%).
The FDA is currently reviewing a new drug application (NDA) for 18F-rhPSMA-7.3 for diagnostic imaging of prostate cancer.3 The NDA is supported by findings from a phase 1 trial and two phase 3 trials, SPOTLIGHT and LIGHTHOUSE. The findings from LIGHTHOUSE have not yet been made available.
At the time of his presentation at ASTRO, Lowentritt also released a statement that was included in a press release announcing the new SPOTLIGHT data.2
“The ability to determine the extent and location of recurrent prostate cancer to inform appropriate clinical management for these men is key for physicians and their patients, because up to 40% of patients who undergo radical prostatectomy, and up to 50% of patients who undergo radiation therapy will develop local or distant recurrences within 10 years,” stated Lowentritt.
“A rising PSA after radical prostatectomy usually precedes a clinically detectable recurrence by years, but cannot differentiate between local, regional, or systemic disease. The utility of conventional imaging for the localization of recurrence is limited, particularly in patients with low PSA levels. Relapse after curative-intent primary treatment remains a considerable clinical burden, and precise imaging techniques are required to identify areas of involvement to facilitate the delivery of optimized patient management. These findings from the SPOTLIGHT study showed high detection rates by majority read for 18F-rhPSMA-7.3 PET over a wide range of baseline PSA levels,” he added.