Citations

81 Background: In the PSMAfore clinical trial, 177 Lu-PSMA-617 achieved a PSA50 (defined as a ≥50% reduction in prostate-specific antigen [PSA] from baseline) response rate in 58%, a median radiographic progression-free survival (PFS) of 12 months, and a median overall survival (OS) of 25 months among taxane-naïve patients with mCRPC who had received one prior androgen receptor pathway inhibitor (ARPI). The aim of the present study was to evaluate the real-world effectiveness of 177 Lu-PSMA-617 in taxane-naïve patients with mCRPC who had received one or more prior ARPIs. Methods: This retrospective, observational study included taxane-naïve adults with mCRPC initiating 177 Lu-PSMA-617 between March 23, 2022, and June 27, 2025, after ≥1 prior ARPI. All data for the study were extracted from the PRECISION data platform, a harmonized dataset of patients with advanced prostate cancer in the US treated in a variety of clinical settings. The index date was the date of 177 Lu-PSMA-617 initiation. Patient characteristics and PSA response rates were evaluated descriptively. PFS, defined as the time from 177 Lu-PSMA-617 initiation to progression or death, was estimated using Kaplan–Meier methodology. Results: A total of 500 patients were included. The median age was 75 years, 75% of patients were White and 8% Black, and 18% were treated in urology centers while 82% were treated in oncology centers. The most common site of metastasis was bone (77%), followed by lymph node (21%), visceral (12%), and unknown (5%). Overall, 51% had received 1 previous ARPI while 49% had received ≥2. The median baseline PSA was 26.7 ng/mL (interquartile range [IQR] 10−105 ng/mL) and the median time from mCRPC diagnosis to 177 Lu-PSMA-617 initiation was 23.6 months. The median number of 177 Lu-PSMA-617 cycles received was 4 (IQR 2−6). Among 219 patients with available PSA measurements both before and during 177 Lu-PSMA-617 treatment (representing 44% of the cohort), PSA response rates were as follows: PSA50 in 137 (63%), PSA80 in 86 (39%), and PSA90 in 56 (26%) patients. Overall, the median PFS was 13.5 months (95% confidence interval 11.7–14.7 months). Conclusions: The effectiveness of 177 Lu-PSMA-617 as a standard-of-care treatment in real-world, taxane-naïve patients with mCRPC who had received prior treatment with ≥1 ARPI is consistent with results from the PSMAfore trial, confirming the applicability of those findings to the real-world population now eligible for 177 Lu-PSMA-617. Further research on sequencing 177 Lu-PSMA-617 after one or more prior ARPIs in taxane-naïve patients with mCRPC is needed to guide optimal treatment sequencing in clinical practice.

79 Background: In March 2025, the indication for 177 Lu-PSMA-617 was expanded to include prostate-specific membrane antigen (PSMA)-positive patients with mCRPC treated with ≥1 androgen receptor pathway inhibitor (ARPI) and considered appropriate to delay taxane-based chemotherapy. With 177 Lu-PSMA-617 moving earlier in the treatment journey, it is important to understand the clinical activity of other systemic therapies after 177 Lu-PSMA-617. The aim of this study was to evaluate the clinical outcomes among patients with mCRPC receiving a systemic therapy after 177 Lu-PSMA-617 treatment. Methods: This retrospective, observational study used real-world data from the PRECISION data platform, a proprietary dataset developed by Novartis representative of patients with advanced prostate cancer in the US from diverse clinical settings. Patients with mCRPC treated with 177 Lu-PSMA-617 who received a systemic therapy ≥14 days after treatment with 177 Lu-PSMA-617 between March 23, 2022, and June 27, 2025, were included. Systemic therapies included ARPIs (abiraterone, enzalutamide, darolutamide, apalutamide); chemotherapy (cabazitaxel, docetaxel, carboplatin, cisplatin, etoposide, mitoxantrone); immunotherapy (pembrolizumab, sipuleucel-T); poly (ADP-ribose) polymerase (PARP) inhibitors (niraparib, olaparib, talazoparib, rucaparib); and radium-223. Patient characteristics and prostate-specific antigen (PSA) response were evaluated descriptively. Progression-free survival (PFS) from subsequent therapy initiation was estimated using Kaplan–Meier methodology. Results: A total of 442 patients receiving any subsequent systemic therapy after 177 Lu-PSMA-617 were included. Overall, 95% of patients received ≥1 ARPI and 76% ≥1 taxane pre- 177 Lu-PSMA-617. The median age was 73 years. Most patients received a taxane (n = 188), an ARPI (n = 176), or a PARP inhibitor (n = 33) as their subsequent therapy. The median time to subsequent therapy initiation was 70 days (interquartile range 38−137 days) from the last 177 Lu-PSMA-617 administration. Among 299 patients receiving a systemic therapy after 177 Lu-PSMA-617 with PSA values available both pre-index and during subsequent treatment, 48% achieved a ≥50% reduction in PSA from baseline (PSA50), 31% a PSA80, and 18% a PSA90. The median PFS from the initiation of subsequent therapy was 8.6 months in the entire cohort; this was 10.7 months with a subsequent ARPI, 7.2 months with a subsequent taxane, and 7.1 months with a subsequent PARP inhibitor. Conclusions: In this real-world analysis, meaningful clinical responses were observed in a subset of patients who received subsequent systemic therapies after 177 Lu-PSMA-617.

Background: Sodium–glucose cotransporter 2 inhibitors (SGLT2i) are nephroprotective but are associated with early eGFR decline, also termed “eGFR dip.” Despite elevated risk of kidney disease, this phenomenon is understudied among people with HIV (PWH). Methods: In a 1:1 propensity score–matched cohort study using data from 9 Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) sites, we compared new SGLT2i users with new users of other antihyperglycemic classes. We estimated adjusted hazard ratios (aHRs) for time to ≥10% and ≥30% eGFR decline using multivariable Cox proportional hazards models and analyzed eGFR change using multivariable linear mixed models. In addition, longer-term eGFR trends over 24 months were visualized using locally weighted scatterplot smoothing (LOWESS) curves. Results: Among 1554 eligible PWH, we obtained 295 matched pairs. Over 6 months, eGFR decline incidence of ≥10% and ≥30% was higher among users of SGLT2i versus other antihyperglycemic classes (58.2% vs. 37.4%; aHR: 1.79; 95% CI: 1.40%–2.28%; and 17.3% vs. 9.8%; aHR: 1.69; 95% CI: 1.05–2.73; respectively). The adjusted mean eGFR change at 6 months was −2.62 mL/min/1.73 m 2 for SGLT2i versus 0.05 mL/min/1.73 m 2 for other classes. Long-term eGFR trends revealed an expected initial decline after SGLT2i initiation, followed by stabilization and a slower subsequent decline compared with other classes. Conclusions: Acute eGFR dips were more common among PWH initiating SGLT2i relative to other antihyperglycemic classes, although overall declines were small, transient, and consistent with the general population. Further research is needed to explore the long-term effects of SGLT2i in PWH.