EMETPRO: A multicenter, international, retrospective analysis evaluating patients (pts) with metastatic hormone-sensitive prostate cancer (mHSPC) with early progression (EP).
Authors: Turco Fabio , Pedrani Martino , Salfi Giuseppe , Mehra Niven , Slootbeek Peter , Labriola Matthew , Broderick Amanda , Patrikidou Anna , Patry Hortense , Buttigliero Consuelo , Uemura Hirotsugu , Utsumi Takanobu , Raggi Daniele , Morales-Barrera Rafael , Guevara Daniela , Caffo Orazio , Zivi Andrea , Barata Pedro C. , Gillessen Silke , Pereira Mestre Ricardo 
Published: February 2025

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Background:
Combination therapies, such as androgen deprivation therapy (ADT) + androgen receptor pathway inhibitor (ARPI) +/- docetaxel, were shown to improve overall survival (OS) in pts with mHSPC. However, some pts are still characterized by EP. EMETPRO study analyzed these pts and their response to treatments administered at progression.
Methods:
EMETPRO is a multicenter, retrospective registry of pts with EP mHSPC defined as pts who have progression ≤ 6 months (m) under combination therapies (ADT + docetaxel or ADT + ARPI) or ≤ 9 m from ADT alone start. The primary endpoint is progression-free survival (PFS) calculated from the start of first-line (1°L) treatment for mCRPC in the entire population and in the different treatments sub-cohorts based on the treatment received in mHSPC. Secondary endpoints included OS calculated from the start of treatment for mHSPC and from the start of 1°L treatment for mCRPC.
Results:
From May 2005 to May 2023 431 pts were enrolled in the study. Median age was 69 years. Molecular analyses were available in 195 (45.2%) pts (Table). 206 (47.8%) pts received ADT alone for mHSPC while 123 (28.6%) and 77 (17.8%) pts received ADT + docetaxel and ADT + ARPI, respectively. 80 (38.8%) and 66 (32.0%) pts treated with ADT alone in mHSPC received ARPI or docetaxel as 1°L mCRPC treatment, respectively. 77 (62.6%) and 13 (10.6%) pts treated with ADT+ docetaxel in mHSPC received ARPI or cabazitaxel in mCRPC, respectively. 46 (59.7%) and 7 (9.1%) pts treated with ADT+ ARPI in mHSPC received docetaxel or a second ARPI in mCRPC, respectively. 14 pts (3.2%) received olaparib or radioligand treatments as 1°L mCRPC therapy. The median PFS from the start of 1°L treatment for mCRPC was 6.5, 4.9, and 5.4 m for pts that received ADT, ADT + docetaxel and ADT + ARPI, respectively. The median OS from mHSPC was 27.0, 20.0, and 19.5 m, in the same groups while the median OS from 1°L treatment for mCRPC was 18.5, 12 and 14.6 m, respectively. The 1°L therapy received in the mCRPC setting and the molecular profile did not correlate with PFS or OS.
Conclusions:
Pts with EP mHSPC are characterized by poor outcomes regardless of treatment received at progression. The best 1°L mCRPC therapy to use in these pts remains a crucial unmet clinical need. Future studies evaluating novel mechanisms (e.g. olaparib or lutetium PSMA) or intensification strategies (e.g. cabazitaxel and/or carboplatin) in this setting are urgently needed.

Baseline characteristics.

Number (N°) of pts
431

GS≥8 at mHSPC, N° (%)
278 (64.5)

High-volume disease (CHAARTEED), N° (%)
302 (70.1)

N° of pts with germline testing results
63

Alterations detected, N° (%)
24 (38.1)

BRCA alterations detected, N° (%)
13 (20.6)

N° of pts with somatic testing results
181

DNA damage response and repair gene alterations, No. (%)
47 (26.0)

At least one TP53/PTEN/RB1 gene mutation detected, No. (%)
84 (46.4)