Citations 2
Race and Outcomes to [177Lu]Lu-PSMA-617 in Advanced Prostate Cancer
Rami, Avina , Zhong, Caiwei , Muniz, Miguel, Khorasanchi, Adam , Fein, Daniel , Stoltenberg, Hailey, Gopalakrishan, Dharmesh, Yang, Yuanquan , Ng, Thomas S.C. , Gafita, Andrei , Jacene, Heather A. , Ravi, Praful , Muniz, Miguel , Khorasanchi, Adam , Fein, Daniel , Ng, Thomas S C , Childs, Daniel S , Xie, Wanling , Gallagher, John F. , Mohammadi, Sedra, Voter, Andrew F. , Childs, Daniel S.
Cancers | June 12, 2025 | Volume: 17 | Issue: 12 | Pages: 1960
Black patients with metastatic prostate cancer have higher mortality rates compared to non-Hispanic White patients. There are no data on outcomes with [177Lu]Lu-PSMA-617 (LuPSMA) across racial groups. We evaluated the association between race and outcomes with LuPSMA in a multi-institutional cohort of consecutive patients with mCRPC treated with LuPSMA. The primary outcomes were PSA-50 rate, PSA-progression-free survival (PSA-PFS), and overall survival (OS). Statistical models were adjusted for age, number of prior therapies, sites of metastases, and baseline PSA. A total of 654 patients were included; 593 (91%) were White, 45 (7%) were Black and 16 (2%) were another non-Black minority (NBM). There were no statistically significant differences in PSA-50 rates, PSA-PFS and OS between the groups. Black and White patients treated with LuPSMA had similar clinical outcomes; efforts are needed to ensure Black and NBM patients have equal access to life prolonging therapies to narrow disparities in outcomes.
Overcoming differential tumor penetration of BRAF inhibitors using computationally guided combination therapy
Ng, Thomas S.C. , Hu, Huiyu , Kronister, Stefan , Lee, Chanseo , Li, Ran , Gerosa, Luca , Stopka, Sylwia A. , Burgenske, Danielle M. , Khurana, Ishaan, Regan, Michael S. , Vallabhaneni, Sreeram, Putta, Niharika, Scott, Ella , Giobbie‐Hurder, Anita , Parangi, Sareh , Agar, Nathalie Y.R. , Jacene, Heather A. , Sullivan, Ryan J. , Buchbinder, Elizabeth I. , Mikula, Hannes , Matvey, Dylan , Kohler, Rainer H , Sarkaria, Jann N , Parangi, Sareh , Sorger, Peter K , Agar, Nathalie Y R , Sullivan, Ryan J , Mikula, Hannes , Weissleder, Ralph , Miller, Miles A , Stopka, Sylwia A , Regan, Michael S , Burgenske, Danielle M , Sarkaria, Jann N. , Miller, Miles A.
Science Advances | April 29, 2022 | Volume: 8 | Issue: 17 | Pages: No page available
BRAF-targeted kinase inhibitors (KIs) are used to treat malignancies including BRAF-mutant non–small cell lung cancer, colorectal cancer, anaplastic thyroid cancer, and, most prominently, melanoma. However, KI selection criteria in patients remain unclear, as are pharmacokinetic/pharmacodynamic (PK/PD) mechanisms that may limit context-dependent efficacy and differentiate related drugs. To address this issue, we imaged mouse models of BRAF-mutant cancers, fluorescent KI tracers, and unlabeled drug to calibrate in silico spatial PK/PD models. Results indicated that drug lipophilicity, plasma clearance, faster target dissociation, and, in particular, high albumin binding could limit dabrafenib action in visceral metastases compared to other KIs. This correlated with retrospective clinical observations. Computational modeling identified a timed strategy for combining dabrafenib and encorafenib to better sustain BRAF inhibition, which showed enhanced efficacy in mice. This study thus offers principles of spatial drug action that may help guide drug development, KI selection, and combination.