Cancer-control outcomes of metastatic castration resistant prostate cancer patients with <i>BRCA</i> -gene or tumor suppressor mutations undergoing 177-lutetium PSMA radioligand therapy.

Abstract

71 Background: Several tumor gene mutations are known for metastatic castration-resistant prostate cancer (mCRPC) are known. The individual response to 177-Lutetium Prostate-specific membrane antigen (Lu-PSMA) therapy is under current investigation regarding the genomic profile of mCRPC patients. Methods: We relied on the FRAMCAP database and compared progression-free (PFS) and overall survival (OS) rates of mCRPC patients with Breast Cancer related antigen ( BRCA ) or tumor suppressor gene mutations ( TP53, PTEN, RB1 [TSG]). Especially, subgroup analyses were performed for Lu-PSMA-treated mCRPC patients. Results: Of 194 mCRPC patients, 22% were BRCA1/2 vs. 14% TSG vs. 63% without one of these mutations. Patients with no mutation harbored significantly lower Gleason score 8-10, relative to BRCA and TSG patients. In PFS analyses of first line mCRPC, no difference between all three groups was observed, while median OS differed significantly with 46.3 vs. 48.7 vs. 95.4 months for BRCA vs. TSG vs. no mutated patients (p&lt;0.05). In univariable Cox regression models, BRCA mutated patients were at higher risk for death (hazard ratio [HR]: 2.57, p&lt;0.01), while TSG patients were not (p=0.4). Of 87 Lu-PSMA treated mCRPC patients, significant differences in PFS and OS were made (both p≤0.02). In univariable and multivariable Cox regression models, BRCA mutated Lu-PSMA patients were at higher risk for death, while TSG patients had similar outcomes as no mutated patients. Conclusions: In real-world setting, substantially lower OS in mCRPC is observed for BRCA and TSG mutated patients, while no difference in first line PFS could be computed. In Lu-PSMA-treated patients, worst outcomes were observed for BRCA patients. Age at mCRPC, years 149 68 (61, 75) 66 (61, 71) 69 (65, 80) 69 (63, 76) 0.3 PSA at CRPC, ng/ml 105 12 (3, 50) 12 (1, 72) 5 (3, 36) 13 (4, 46) 0.8 Treatment lines mCRPC 194 3.00 (1.00, 4.00) 3.00 (1.00, 4.50) 3.00 (1.00, 4.00) 3.00 (1.00, 4.00) 0.6 ECOG status at mCRPC 79 0.017 0 47 (59%) 7 (44%) 12 (92%) 28 (56%) 1 32 (41%) 9 (56%) 1 (7.7%) 22 (44%) ≥2 0 (0%) 0 (0%) 0 (0%) 0 (0%) Cardiovascular disease 168 52 (31%) 9 (23%) 6 (21%) 37 (37%) 0.15 Gleason Score 179 0.032 8-10 130 (73%) 34 (83%) 22 (81%) 74 (67%) De Novo mHSPC 186 123 (66%) 32 (76%) 18 (64%) 73 (63%) 0.3 High volume mHSPC 126 73 (58%) 24 (71%) 12 (63%) 37 (51%) 0.13 Metastatic sites at mCRPC 92 0.2 M1a 6 (6.5%) 1 (4.5%) 2 (10%) 3 (6.0%) M1b 75 (82%) 15 (68%) 17 (85%) 43 (86%) M1c 11 (12%) 6 (27%) 1 (5.0%) 4 (8.0%) PARPi Treatment 194 25 (13%) 15 (35%) 1 (3.6%) 9 (7.3%) &lt;0.01 1 Median (IQR); n (%). 2 Kruskal-Wallis rank sum test; Fisher’s exact test; Pearson’s Chi-square test.