Abstract
1604P PSMA-targeted radioligand therapy (RLT) with 131I-LNTH-1095 (1095) plus enzalutamide (enza) vs enza alone in chemotherapy-naïve patients (pts) whose piflufolastat F 18-avid metastatic castration-resistant prostate cancer (mCRPC) progressed on abiraterone (abi): ARROW
Annals of oncology, Vol.35(Supplement 2), pp.S967-S968
09/2024
DOI: 10.1016/j.annonc.2024.08.1685
Abstract
Background
In nonclinical studies, prostate-specific membrane antigen (PSMA)-targeted RLT plus androgen antagonist had synergistic cytotoxic effects on prostate cancer (PCa) cells.
Methods
ARROW recruited mCRPC pts (≥18 years) who were to receive enza after progression on abi. mCRPC was confirmed by histopathology and PSMA-PET avidity (piflufolastat F 18), while RECIST 1.1 and Prostate Cancer Working Group 3 (PCWG3) criteria were applied. Pts were randomized 2:1 to either enza (160 mg QD) plus 1095 (100 mCi dose, then up to 4 cycles ≥8 weeks apart, as determined by dosimetry and dose-limiting events) or enza. The primary endpoint was prostate-specific antigen response rate (PSA RR): first occurrence of ≥50% decline in PSA from baseline, confirmed by a second measurement ≥3 weeks later. Secondary endpoints included radiographic-progression–free survival (rPFS), overall response rate (ORR), landmark overall survival (OS), PSA progression (PCWG3 criteria), duration of response, & safety. The primary endpoint assumed a RR of 59% for 1095+enza and 30% for enza. With 2:1 randomization and anticipated 15% dropout, ≥102 pts were needed to provide 80% power for a 2-sided χ2 test (α=0.05). A 2-sided Cochran-Mantel-Haenszel χ2 test stratified by risk category was used for the primary endpoint.
Results
Of 177 screened pts, 120 were randomized to enza+1095 (n=80) or enza (n=40). Patient characteristics in both arms were similar at baseline. PSA RR was 62.86% for enza+1095 pts vs 31.25% for enza pts (p=0.0025). Median rPFS was 14.0 months (95% CI: 8.64-18.20) for enza+1095 vs 11.5 months (2.79-18.43) for enza (p=0.1032). Incidence of TEAEs of grade ≥3 was 65.8% (enza+1095) vs 41.0% (enza). Most frequent TEAEs for enza+1095 vs enza, respectively, were fatigue (75.0%, 53.8%), nausea (59.2%, 33.3%), and decreased appetite (48.7, 17.9%).
Conclusions
There was statistically and clinically significant improvement in PSA RR for enza+1095 vs enza alone.
Details
- Title: Subtitle
- 1604P PSMA-targeted radioligand therapy (RLT) with 131I-LNTH-1095 (1095) plus enzalutamide (enza) vs enza alone in chemotherapy-naïve patients (pts) whose piflufolastat F 18-avid metastatic castration-resistant prostate cancer (mCRPC) progressed on abiraterone (abi): ARROW
- Creators
- E.Y. Yu - Fred Hutch Cancer CenterV. Narayan - University of PennsylvaniaG. Esposito - MedStar Georgetown University HospitalR. Szmulewitz - University of ChicagoY. Lu - The University of Texas MD Anderson Cancer CenterM. Lilly - Medical University of South CarolinaJ. Calais - University of California, Los AngelesG. Bratslavsky - SUNY Upstate Medical UniversityM. Vasanawala - Nucl, VA Palo Alto Healthcare System, Palo Alto, CA, USAG.A. Ulaner - Hoag Memorial Hospital PresbyterianF. Pouliot - Université LavalD. Laidley - London Health Sciences CentreN. Fleshner - Princess Margaret Cancer CentreF. Saad - Urology Department, Centre Hospitalier de Universite to Montréal (CHUM), Montreal, QC, CanadaY. Menda - University of Iowa
- Resource Type
- Abstract
- Publication Details
- Annals of oncology, Vol.35(Supplement 2), pp.S967-S968
- DOI
- 10.1016/j.annonc.2024.08.1685
- ISSN
- 0923-7534
- Publisher
- Elsevier Ltd
- Language
- English
- Date published
- 09/2024
- Academic Unit
- Radiology; Radiation Oncology
- Record Identifier
- 9984704828802771
Metrics
46 Record Views