A study recently published in the Lancet Oncology suggested that nomograms could predict outcomes with the targeted agent PSMA Lutetium-177-PSMA-617 (177Lu-PSMA) in patients with metastatic castration-resistant prostate cancer (mCRPC).1
Researchers used data from 2 previous phase 2 studies (NCT03042312, ACTRN12615000912583) to retrospectively assess patients who had been treated with 177Lu-PSMA for overall survival (OS) and progression-free survival (PFS) of prostate specific antigen (PSA).
âThese externally validated nomograms which predict the results after 177Lu-PSMA in mCRPC patients could aid in clinical trial design and individual clinical decision making, particularly in settings where 177Lu-PSMA is being touted as a new therapeutic option, âwrote study researchers led by Andrei Gafita, MD, of the University of California, Los Angeles.
This study population consisted of 270 patients who were divided into 2 cohorts for nomogram development (n = 196) and independent validation (n = 74). Forty patients (10%) started treatment after the cut-off date, 86 (21%) received 18F-labeled PSMA-PET and 9 (2%) were lost to follow-up.
Of the total cohort examined, 113 patients were included in a clinical trial compared to 157 patients who received 177Lu-PSMA as part of a humanitarian access program. Treatment was administered for a median of 3 cycles per patient, each cycle comprising a single injection of 177Lu-PSMA at 6.0-8.5 GBq every 6-8 weeks. Previous treatment in 257 patients included second generation antiandrogens while 219 had experience with chemotherapy.
The primary endpoints were PSA-PFS and OS with a secondary endpoint of 50% decrease in PSA (PSA50) or more from baseline during treatment.
Some predictors used to assess OS were time since initial diagnosis of prostate cancer, chemotherapy status, baseline hemoglobin concentration, and PET / CT characteristics. PSA-PFS was defined as the time between treatment and PSA progression or death.
The median duration of follow-up was 21.5 months. At the last follow-up, 225 patients had died and 245 had presented with progression of PSA. Median OS and PSA-PFS were similar between cohorts, with OS rates at 12 and 18 months of 54% and 34%, respectively, for all patients.
The estimated rate of PSA-PFS at 3 months was 64%, while at 6 months it was estimated at 38%,
Patients in the cohorts were described as having high or low risk disease and based on an optimal cutoff calculated in the risk score of 197 points for the OS nomogram and 178 points for the PSA-PFS nomogram. In the low-risk patients of the development cohort, the median OS was 19.1 months compared to 8.4 months in the high-risk patients (P <.0001 the median os for low-risk patients in validation cohort was months versus high-risk>P <.0001 in the entire cohort os for low risk was months and high>P <.0001>
177Lu-PSMA in low- and high-risk patients resulted in a median PSA-PFS of 9.4 and 3.3 months, respectively, in the development cohort (P <.0001 months and in the validation cohort>P = .022); and 8.8 months against 3.3 months in the whole cohort (P <.0001>
For the secondary endpoint of PSA50, the area under the curve for the validation cohort was 0.78%. The investigators used a threshold of 41 points for stratification, which gave a sensitivity of 94% and a specificity of 38% to determine responders or non-respondents. The positive predictive value was 54% and the negative predictive value was 89%.
âOur nomograms support the preclinical results and suggest that high levels of tumor PSMA expression are a prerequisite for a favorable outcome after 177Lu-PSMA (higher expression of PSMA is associated with longer overall survival and progression-free survival of PSA, and a 50% greater likelihood of PSA decline), âthe investigators wrote. study.
1. Gafita A, Calais J, Grogan TR, et al. Nomograms for Predicting Outcome After 177Lu-PSMA Treatment in Men With Metastatic Castration-Resistant Prostate Cancer: A Multicenter International Retrospective Study [published online ahead of July 8, 2021]. Lancet Oncol. doi: 10.1016 / S1470-2045 (21) 00274-6