- Results of the multi-center, international phase 3 TALAPRO-2 trial show that the combination of PARP inhibitor talazoparib plus anti-androgen enzalutamide versus standard treatment with enzalutamide significantly improved overall survival in patients with metastatic castration-resistant prostate cancer (mCRPC).
- Final overall survival analysis demonstrated an 8.8-month improvement in median overall survival and a 20.4% reduction in risk of death in patients assigned to the novel combination compared with patients who received standard therapy plus placebo.
- Co-authored by Joan Carles of the Vall d’Hebron Institute of Oncology (VHIO), these findings have been presented at the 2025 ASCO Genitourinary Cancers Symposium by first author Neeraj Agarwal, Senior Director of Clinical Research of the Huntsman Cancer Institute in the U.S.
The multicenter, international, randomized phase 3 TALAPRO-2 trial was designed to evaluate the combination of poly ADP ribose polymerase inhibitor (PARPi) talazoparib and androgen receptor pathway inhibitor (ARPI) enzalutamide versus standard-of-care enzalutamide plus placebo in patients with metastatic castration-resistant prostate cancer (mCRPC).
Presented by first author Neeraj Agarwal at the 2025 ASCO Genitourinary Cancers Symposium (ASCO GU)(1), February 13-15, San Francisco, results of final overall survival analysis show that treatment with talazoparib plus enzalutamide significantly improved overall survival (OS) compared with standard-of-care enzalutamide. At a median follow up of 52.5 months, data show a 20.4% reduction in risk of death and 8.8-month improvement in median OS in patients assigned to the novel combination.
With an estimated 1.5 million new cases and 397,000 deaths worldwide in 2022, prostate cancer ranks second as the most frequent cancer globally and the fifth leading cause of cancer death among men(2) .
Metastatic castration-resistant prostate cancer (mCRPC) is a cancer that has spread beyond the prostate gland and has progressed despite medical or surgical treatment to lower testosterone.
“When prostate cancer is diagnosed early the prognosis is generally very good, with high cure rates. However, in men newly diagnosed with late-stage prostate cancer, the median overall survival is less than three years. Lengthening and improving survival in this patient population therefore represents an unmet clinical need,” said Joan Carles, Head of the Genitourinary, CNS, and Sarcoma Tumors Program at the Vall d’Hebron University Hospital, co-leader of VHIO’s Prostate Cancer Group, and a co-author of this present study.
PARPi in patients unselected for alterations in DNA damage repair genes
Alterations in DNA damage repair genes involved in homologous recombination repair (HRR) occur in 30% of mCRPC and associate with increased sensitivity to treatment with PARPi.
“Preclinical evidence suggests that patients with metastatic castration-resistant prostate cancer without these gene alterations could also benefit from treatment with PARPi when combined with an androgen receptor pathway inhibitor,” added Carles.
TALAPRO-2 included 805 patients with mCRPC whose tumor samples were prospectively assessed for homologous recombination repair (HRR) gene alterations, results of which did not condition their participation in the study.
At a median follow up of 52.5 months, median overall survival was 45.8 months in patients who received the combination of talazoparib and enzalutamide, versus 37 months in patients assigned to standard treatment.
“ Joan Carles said.
“Based on these data and upon evaluation by the different regulatory authorities and healthcare reimbursement systems, the combination of talazoparib plus enzalutamide should be a new standard of care in men with first-line metastatic castration-resistant prostate cancer,” he concluded.
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References
- 2025 ASCO Genitourinary Cancers Symposium corresponding session details
Track: Prostate Cancer – Advanced | Prostate Cancer – Localized
Type: Oral Abstract Session
Location: Level 3, Ballroom | Live Stream
Date: 13 February, 2025
Time: 17:00 CET
Chairs: Kosj Yamoah, MD, PhD, H. Lee Moffitt Cancer Center and Research Institute; Channing Judith Paller, MD The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins.
Final overall survival (OS) with talazoparib (TALA) + enzalutamide (ENZA) as first-line treatment in unselected patients with metastatic castration-resistant prostate cancer (mCRPC) in the phase 3 TALAPRO-2 trial.
Neeraj Agarwal, Arun Azad, Joan Carles, Andre P. Fay, Nobuaki Matsubara, Cezary Szczylik, Ugo De Giorgi, Jae Young Joung, Peter C. Fong, Eric Voog, Robert J. Jones, Neal D. Shore, Curtis J. Dunshee, Stefanie Zschaebitz, Jan Oldenburg, Xun Lin, Cynthia Healy, Matko Kalac, Dana A. Kennedy, Karim Fizazi.
Presentation number: LBA18
2. Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, Jemal A. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024 May-Jun;74(3):229-263.
