Prostate-specific membrane antigen (PSMA) expression in patients with metastatic triple negative breast cancer: Initial results of the PRISMA study.

Guilherme Nader Marta Academic Trials Promoting Team, Institut Jules Bordet and l’Université Libre de Bruxelles (U.L.B), Brussels, Belgium info_outline Guilherme Nader Marta, Zena Wimana, Loubna Taraji, Gabriela Critchi, Philippe Georges Aftimos, Martine J. Piccart-Gebhart, Patrick Flamen, Geraldine Gebhart

Authors Guilherme Nader Marta Academic Trials Promoting Team, Institut Jules Bordet and l’Université Libre de Bruxelles (U.L.B), Brussels, Belgium info_outline Guilherme Nader Marta, Zena Wimana, Loubna Taraji, Gabriela Critchi, Philippe Georges Aftimos, Martine J. Piccart-Gebhart, Patrick Flamen, Geraldine Gebhart Organizations Academic Trials Promoting Team, Institut Jules Bordet and l’Université Libre de Bruxelles (U.L.B), Brussels, Belgium, Nuclear Medicine Department, Institut Jules Bordet and l’Université Libre de Bruxelles (U.L.B), Brussels, Belgium, Brussels, Belgium, Nuclear Medicine Department, Institut Jules Bordet and l’Université Libre de Bruxelles (U.L.B), Brussels, Belgium, Brussel, Belgium, Medical Oncology Department, Institut Jules Bordet and l’Université Libre de Bruxelles (U.L.B), Brussels, Belgium, Brussels, Belgium, Medical Oncology Department, Institut Jules Bordet and l'Université Libre de Bruxelles, Brussels, Belgium Abstract Disclosures Research Funding Other Association Jules Bordet Background: Radioligand therapy (RLT) targeting prostate-specific membrane antigen (PSMA) prolongs survival of patients (pts) with prostate cancer. Preliminary immunohistochemistry (IHC)-based studies suggest that PSMA is highly expressed in triple negative breast cancer (TNBC). The PRISMA study aims to assess PSMA expression in pts with metastatic TNBC (mTNBC) via positron-emission tomography/computed tomography (PET/CT) to evaluate the feasibility of PSMA-targeted RLT for TNBC. Methods: PRISMA is a prospective, single-center study that enrolled pts with progressive mTNBC and measurable disease on 18F-FDG PET/CT to undergo 68Ga-PSMA-11 PET/CT. TNBC definition (ASCO/CAP) was based on the IHC of the primary breast cancer (BC) or metastasis. Target lesions (TL) were defined as metastatic lesions ≥1.5 cm with significant uptake in 18FDG-PET/CT. The same TL regions were propagated to the 68Ga-PSMA-PET/CT. 68Ga-PSMA-11 maximum standard uptake value (SUVmax) was measured for each TL. PSMA patterns A and B were defined according to presence of a majority (pattern A) or a minority (pattern B) of positive TL on 68Ga-PSMA (ie. uptake greater than that of normal liver parenchyma). Mann-Whitney U test was used to assess differences in median SUVmax (mSUVmax) between subgroups. Results: Ten pts with progressive mTNBC were enrolled. One pt was excluded due to lack of TL on 18FDG-PET/CT. Median age was 48 years (range 36-68), median number of TL per patient was 8 (5-18). Five pts had a TNBC IHC since the initial BC diagnosis, while 4 had a switch to TNBC (4 with initial estrogen receptor [ER]-positive and 1 with HER2-positive BC). All evaluable pts had inter- and intra-organ heterogeneity in PSMA uptake in TL and 2 pts had some mismatch with FDG-positive and PSMA-negative TL. mSUVmax was 2.99 (range 1.7-6.3) in the overall population and was higher in pts with pattern A (5.1 vs 2.6 in patterns A and B, respectively, p = 0.03). mSUVmax was numerically higher in younger pts (5.0 vs 2.6 in pts <50y and ≥50y, p = 0.28), PD-L1-positive (5.0 vs 2.7 in PD-L1-positive and -negative, p = 0.14), de novo metastatic disease (5.0 vs 2.9 in de novo and recurrent BC, p = 0.38) and those with ER-negative primary breast tumor (3.4 vs 3.0 in ER-negative and ER-positive primary BC, p = 0.9). Conclusions: A significant PSMA uptake was observed in a proportion of pts with mTNBC. Inclusion of additional pts and translational analyses will allow the identification of PSMA expression determinants. PSMA-targeted RLT may be considered as an innovative therapeutic strategy to be explored in selected pts with mTNBC. Pts ID Stage at diagnosis Treatment lines PD-L1 PSMA pattern mSUVmax (range) 1 IV 1 Pos A 5.0 (1.7-16.0) 2 I 2 Neg B 2.7 (1.8-5.3) 3 II 3 Neg B 1.7 (0.7-3.9) 4 II 2 - B 2.2 (2.0-5.0) 5 IV 5 Pos A 6.3 (1.9-9.6) 7 III 1 Neg A 3.0 (1.2-7.2) 8 IV 1 Pos B 2.6 (1.5-4.7) 9 III 4 Pos A 5.2 (2.5-7.6) 10 II 3 Pos B 4.1 (1.0-7.6)