BARCELONA, Spain ― Using 177Lu-PSMA (prostate-specific membrane antigen) SPECT to show tumor effect astatine week 12 aft the 3rd dose of the targeted radioligand 177Lu-PSMA-617 (Pluctivo, Novartis) has imaginable arsenic an aboriginal predictive biomarker for men with end-stage metastatic castration-resistant prostate cancer (mCRPC), according to information reported astatine the European Association of Nuclear Medicine (EANM) 2022 meeting.
The aforesaid researcher suggests that 177Lu-PSMA SPECT, if utilized adjacent earlier, aft lone 6 weeks, mightiness besides beryllium a reliable biomarker.
Such aboriginal imaging biomarkers mightiness assistance find intensification oregon deintensification of therapy to the payment of patients for whom clip and prime of beingness person added importance.
For the week-12 study, Louise Emmett, MD, PhD, manager of theranostics and atomic medicine astatine St. Vincent's Hospital Sydney, successful Australia, utilized SPECT to measure effect to 177Lu-PSMA-617 successful LuPIN, a signifier 1/2 proceedings of a operation of 177Lu-PSMA-617 with the added radiation sensitizer NOX66 (idronoxil) successful men with mCRPC.
"177Lu-SPECT-CT has imaginable arsenic a biomarker successful these patients with end-stage disease, but this needs to beryllium validated successful a larger fig of patients and successful operation with different biomarkers, specified arsenic prostate-specific antigen [PSA] and CT," remarked Emmett successful an interrogation with Medscape Medical News.
Essentially, Emmett and colleagues recovered that an summation successful full tumor measurement (TTV) connected quantitative 177Lu-SPECT/CT astatine 12 weeks (or commencement of rhythm three) of attraction with 177Lu-PSMA-617 predicted shorter progression-free endurance (PFS), suggesting 177Lu-SPECT/CT whitethorn play a aboriginal relation arsenic an imaging effect biomarker.
In email correspondence with Medscape Medical News, Andrei Gafita, MD, a atomic medicine doc from UCLA Jonsson Comprehensive Cancer Center, Los Angeles, California, noted the "very important taxable of attraction effect assessment."
"Dr Emmet's enactment showed that 177Lu-PSMA SPECT has large imaginable to go a biomarker that could alteration aboriginal effect valuation to 177Lu-PSMA radioligand therapy," helium noted, adding, "It whitethorn greatly payment peculiarly institutions wherever PSMA-PET/CT is not disposable oregon not reimbursed for the intent of effect evaluation."
Ken Herrmann, MD, subordinate prof of atomic medicine astatine the University of Duisburg-Essen, Germany, besides commented connected the biomarker study. "Establishing quantitative post-177Lu PSMA medication SPECT arsenic a caller surrogate marker for assessing effect to attraction has imaginable upsides, including the imaginable replacement of interim and post-therapy PSMA PET ― which is cost-saving, radiation exposure–saving, and is much convenient, arsenic good arsenic improving therapy guidance, specified arsenic determining whether a therapy holiday, continuation oregon discontinuation is warranted.
"I'm personally intrigued and excited successful this approach," helium said.
Adding NOX66 ― a Radiation Sensitizer ― to 177Lu-PSMA-617
Regarding the prolonging of the attraction effect of 177Lu-PSMA-617, Emmett, who is simply a physician-researcher, explained that "177Lu-PSMA-617 is truly good, but it conscionable doesn't enactment for each patients, and it doesn't enactment agelong enough. These men — and immoderate are rather young — dice excessively soon, and this happens again and again," she said successful explaining what made this proceedings truthful important to her.
177Lu-PSMA-617 unsocial improved wide endurance with efficacy equivalent to that of cabazitaxel chemotherapy. It was approved by the US Food and Drug Administration successful March 2022 for PSMA-positive mCRPC successful operation with a PSMA imaging cause for prime patients. However, radiation absorption remained successful a subset of men and was apt the cardinal operator successful attraction failure, she explained.
In an effort to tackle this radiation resistance, NOX66 was added to attraction with 177Lu-PSMA-617. Safety and efficacy were monitored by clinical, blood-based, and imaging biomarkers.
Biomarkers to Determine Treatment Success oregon Failure Earlier
In the study, 56 men underwent introduction and exit fluorodeoxyglucose (FDG) and PSMA PET, and a PSMA SPECT (single-photon emanation CT) astatine each rhythm (24 hours aft each therapy dose). They received up to six doses of 177Lu-PSMA-617 (7.5 GBq) connected time 1 successful operation with a NOX66 suppository connected days 1–10 of each 6-week cycle.
The mean property of the men was 61 years. The mean PSA level astatine rhythm 1 was 115 (46–476). All men had received anterior docetaxel and 91% cabazitaxel, and 66% had astatine slightest 20 metastases.
"These were men who were pulled retired of palliative care," noted Emmett.
LuPIN recovered that erstwhile the men received the operation of 177Lu-PSMA-617 positive NOX66, the median PSA 50% effect complaint was 61%, with 86% showing immoderate PSA response. Median PFS was 7.5 months (6–9), and median wide endurance was 19.7 months (10–30).
Emmett past conducted the biomarker subanalysis to find whether quantitative parameters connected serial 177Lu-SPECT/CT imaging 24 hours aft a dose of 177LuPSMA-617 were predictive of attraction effect and PFS.
All lesions that were quantitatively identified were manually reviewed, and the physiologic enactment was determined. TTV, standardized uptake worth (SUV) max, and SUVmean were derived.
"We wanted to cognize if the [differences successful the] images betwixt the archetypal injection dose representation [177Lu-SPECT/CT imaging] and the 3rd dose representation could assistance america foretell the diligent outcome," Emmett told Medscape Medical News.
In presumption of SPECT imaging, information from 32 of the 56 patients were analyzable astatine baseline and astatine week 12.
Of these data, SPECT-TTV was reduced betwixt baseline and week 12 successful 68%, portion it accrued successful 31%. An summation of 30% oregon much successful SPECT-TTV by week 12 was seen successful 19%, reported Emmett.
Again, implicit the 12 weeks, SUVmax decreased betwixt baseline and week 12 successful 91%, and SUVmean decreased successful 84%.
Comparing the changes successful SPECT-TTV with PFS (to assistance find the relation of SPECT successful predicting response), Emmett recovered that immoderate summation successful SPECT-TTV betwixt baseline and week 12 was associated with importantly worse PSA-PFS — implicit fourfold worse (hazard ratio [HR], 4.1; 95% CI, 1.5 – 11.2).
The median PSA-PFS successful those with an summation successful SPECT-TTV was 4.5 months (95% CI, 2.8 – 5.6), compared to 7.1 months (95% CI, 6.3 – 10.7) for those successful whom determination was nary summation successful SPECT-TTV.
Alternatively, an summation successful SPECT-TTV of astatine slightest 30% was associated with shorter PSA-PFS (HR, 3.3; 95% CI, 1.3 – 8.6). Also, those patients (8/32) who showed progression successful their PSA astatine week 12 had a importantly worse PSA-PFS (HR, 26.5; 95% CI, 5.4 – 131).
When the PSMA-PET measurement was compared to the SPECT, determination was a beardown correlation betwixt PSMA-PET TTV and the baseline 177Lu-SPECT TTV (R = 0.87; 95% CI, 0.74 – 0.93).
RESPECT Study ― Prediction After Two Treatments ― Week 6
In a precocious published study by Emmett and colleagues, findings were akin successful a cohort of 130 patients, confirming that "decisions astir attraction readying tin beryllium made astatine the 6-week people and not hold until the 12-week mark," she asserted.
She suggested further questions that needed research. "We cognize we can't place precise tiny lesions with SPECT compared to PET, but is that important erstwhile we're looking astatine interim effect biomarkers?" she said.
In conclusion, she said that 177Lu-SPECT-CT seems to person beardown imaginable arsenic a predictive biomarker successful radionucleotide therapy for men with mCRPC, but the results request to beryllium validated successful larger cohorts.
On the valuation astatine 6 weeks, Gafita added that "further probe volition archer america much whether 177Lu-PSMA SPECT performed astatine 6 weeks tin connection guidance for clinicians successful the decision-making process for diligent management."
Also reflecting connected the survey was Christoph Rischpler, MD, atomic medicine specializer astatine University of Duisburg-Essen, Germany, who said that SPECT imaging aft 177Lu-PSMA radioligand therapy is simply a modular process that is casual to execute but that much probe connected usage of the method arsenic a biomarker was needed.
"There are constricted information connected whether this imaging method allows appraisal of attraction efficacy portion therapy is inactive successful advancement and allows conclusions to beryllium drawn astir diligent outcomes," helium said. "This survey highlights the value of SPECT imaging aft 177Lu-PSMA radioligand therapy, since expanding full tumor measurement during therapy was associated with shorter PFS. Thus, a alteration successful therapeutic regimen owed to nonresponse to 177Lu-PSMA therapy could hap earlier."
Emmett, Herrmann, and Gafita person disclosed nary applicable fiscal relationships. Rischpler has received talker honoraria from Adacap, Alnylam, BTG, Curium, GE Healthcare, Pfizer, Siemens Healthineers; has served successful a consultancy relation for Adacap Adacap (now called Novartis Radiopharmaceuticals sells Pluvicto successful the US) and Pfizer, and has received a probe assistance from Pfizer.
European Association of Nuclear Medicine (EANM) 2022: Abstract OP-158. Presented October 16, 2022.
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