TMPRSS2-EG in MCRPC |
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The presence of TMPRSS2-EG Fusions in the circulating tumor DNA (CTDNA) included, among other things, with differential generation frequency, tumor mutation pollution (TMB) and gene expression signatures in patients with metastatic castration-resistant prostate cancer (MCRPC) (MCRPC) after a post-hoc analysis of the phase-3 studies (NCT0395) in patients with metastatic castration resistant (NCT0395) (NCT03395) (NCT03395). 2025 AACR annual conference.1
The results showed that the CTDNA burden was higher in the presence of TMPRSS2-EGwith medium tumor fraction values of 0.22 and 0.11 in which with (n = 97) or without (n = 584) the marker ((n = 584) (or withoutP TMPRSS2-EG, although in patients with VS without a slightly higher median value was observed TMPRSS2-EGAt 3.79 MUT/MB compared to 2.53 MUT/MB. The respective mean values were 4.16 and 4.44 (P = .0003).
“In Talapro-2 the presence of TMPRSS2-EG In CTDNA, a pronounced tumorolecular landscape is connected, including positive association TP53 Changes, negative association with Spop Changes as well as emergency and WNT-Beta-Catenin-Pathway activation, ”wrote Xinmeng Jasmine MU, senior study author and director of computer biology at Pfizer, and co-authors. [Xtandi] Against placebo plus enzalutamide in patients with patients TMPRSS2-EG In CTDNA, considering the high prevalence of TP53 Changes in this sub -group. “
Talapro-2 test background and exploration analysis justification
The double-blind, randomized, placebo-controlled, global Talapro-2 study evaluated the combination of Talazoparib Plus Enzalutamide against Placebo plus enzalutamide in sequentially enrolled cohorts of patients with MCRPC (n = 399) or non-selected (n = 805) homologically repair repair (HRR) -Repair (HRR) (HRR) repairs (HRR) repairs (HRR) changes.
Previously, the combination of Talazoparib and Enzalutamide led to a statistically significant improvement in radiological progression-free survival (RPFS; HR, 0.667; 95% CI, 0.551-0.807; P P = 0.0155) against placebo plus enzalutamide in patients with MCRPC.2 The combination was later approved by the FDA to treat patients with HRR gene -mutated MCRPC Based on earlier results of Talapro-2, which show improved RPFs in this population (HR 0.45; 95% CI, 0.33-0.61; P 3
An earlier evaluation of non-HRR gene changes has also shown a connection between the presence of TMPRSS2-EG In CTDNA and improved results with Talazoparib and Enzalutamide for placebo plus enzalutamide. TMPRSS2-EG In the case of advanced prostate cancer, mergers are often found in 13% of the plasma CCTDNA and 38% of the tumor tissue samples, according to the Foundation Medicine database. A similar frequency was found in the non-selected Talapro-2 population in 14% in CTDNA and 30% in the tumor fabric.
With this information, the researchers assessed the relationship between CTDNA changes and tumor's expression with the presence of TMPRSS2-EG In the non-selected cohort of the patients inscribed in Talapro-2.
Study methods and generation of gene to change
The data, which were rated retrospectively for this analysis, comprised prospectively collected plasma CTDNA from the non-selected TalaPro-2 population. The analysis was based on the security population (n = 681) for all genomic analyzes, whereby the change prevalence that used the intention to do the intention (Itt; n = 687) used. The gene changes were identified by a clinical study -Assay based on the Foundationon -fluid CDX and were characterized as well -known or probably pathogenic variants. The transcriptom data of archive/basic tumor were created using the oncology biomarker panel from HTG, whereby 10 additional genes that are involved in the sensitivity of the PARP inhibitor are involved (n = 304).
The data section for the analysis was August 16, 2022.
TMPRSS2-EG Fusions were found in 14% (n = 98) of the non-selected Talapro-2-top population (n = 687).
“Several genes involved in the pathobiology of prostate cancer … showed imbalances in change status in patients with TMPRSS2-EG vs without TMPRSS2-EG in CTDNA, ”wrote the authors. Patients with TMPRSS2-EG Also had changes in TP53 (61%)Ar (55%)Pten (34%)ATM (8%)APC (11%)BRCA2 (12%)Spop (0%)CDK12 (1%)Present And Ml2 (6%). Patients without TMPRSS2-EG (n = 589) had a lower frequency of changes in TP53 (34%; P Ar (30%; P Pten (13%; P ATM (11%; P = .48)APC (8%; P = .24)BRCA2 (6%; P = .027)Spop (7%; P = .002)CDK12 (7%; P = .032)and MLL2 (6%; P = .82).
Further information on a different tumorolecular landscape
Additional results showed that the tumor transcript, which was increased in patients with (n = 43) without (n = 242), was strongest. TMPRSS2-EG Was with median values of 12.25 counts/million (CPM) or 8.85 cpm (or 8.85 cpm ()P Parp1, BaiaP3, Col2a1 and CBLC were also observed during the evaluation.
Finally, the analysis of the gene expression signature showed that emergency and WNT-Beta-Catenin paths in patients with tumors who accommodate the tumors' dating were activated differently TMPRSS2-EG.
Mu found that the restrictions of the study, apart from the fact that they are retrospective and exploratory nature, encompassed a low CTDNA in some patients and do not adapt to several statistical comparisons.
Opener: No information was listed for MU.
Read more data from the 2025 AACR annual conference around Talazoparib and Enzalutamidee.
References
- Mu XJ, Piulats JM, Laird ad, et al. Investigation of the molecular tumor landscape associated with TMPRS2-EG: a post-hoc analysis from the phase 3-talapro-2 study with first-line (1l) Talazoparib (Tala) + Enzalutamide (Enza) against placebo (PBO) + Enza for metastical castriatant prostatation cancer (MCRPC). Presented at: 2025 AACR annual meetings; 25 to April 30, 2025; Chicago, il. CT102.
- Agarwal N, Azad A, Carles J, et al. The final overall survival (OS) with Talazoparib (Tala) + Enzalutamide (Enza) as a first-line treatment in non-selected patients with metastatic castration-resistant prostate cancer (MCRPC) in the phase 3 Talapro-2 study. J Clin Oncol. 2025; 43 (Suppl 5): LBA18. DOI: 10.1200/JCO.2025.43.5_suppl.lba1
- The FDA approves Talazoparib with enzalutamide for prostate cancer with HRR-gene-mutated metastatic-resistant prostate cancer. FDA. June 20, 2023. Access April 28, 2025.