With almost 1.4 million estimated new cases and 375,000 deaths worldwide, prostate cancer is the second most frequent cancer and the fifth leading cause of cancer death among men in 2020 (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. mCRPC encompasses a heterogeneous, broad range of molecular characteristics and confers a high risk of progression. Approximately 10%–20% of prostate cancer patients develop mCRPC within 5−7 years of diagnosis (3).
The development of more effective treatment strategies targeting the molecular specificities and therapeutic vulnerabilities of this disease will ultimately improve clinical outcomes and quality of life in this patient population. The TALAPRO-2 two-part, two-cohort randomized clinical trial is the first phase III study to combine talazoparib, an oral ADP-ribose polymerase (PARP) inhibitor that plays a role in DNA damage repair, with enzalutamide, an androgen receptor signaling inhibitor, as first-line treatment for patients with mCRPC.
“Data from the first cohort evaluating this combination in unselected patients for genetic alterations in DNA damage repair pathways, previously showed that talazoparib plus enzalutamide versus standard treatment with enzalutamide and placebo significantly improved progression-free survival (4). These results were presented at the 2023 ASCO Genitourinary Cancers Symposium last March,” says Joan Carles, Principal Investigator of the Vall d’Hebron Institute of Oncology’s (VHIO) Genitourinary, Central Nervous System (CNS) Tumors, Sarcoma and Cancer of Unknown Primary Site Group, and a co-author of this present study (1).
Presented today by first author Karim Fizazi, Medical Oncologist at the Institut Gustave Roussy, Villejuif (France), at the 2023 Annual Meeting of the American Society of Clinical Oncology (ASCO) (1), 2-6 June (Chicago, IL), ) and published in parallel in The Lancet (2), results of the TALAPRO-2 prespecified, independent analysis of mCRPC patients harboring homologous recombination repair (HRR) gene alterations from cohorts one and two support the combination of talazoparib plus enzalutamide as first-line treatment for these patients.
Enrolling at total of 399 patients, 200 received the combination of talazoparib plus enzalutamide and 199 patients were treated with standard of care enzalutamide and placebo. In those patients treated with the novel combination, the investigators observed a statistically significant and clinically meaningful radiographic progression free survival over standard of care, and a 55% reduction in the risk of progression or death.
“While overall survival data were not definitive, results point to a favorable trend in patients treated with the novel combination. We observed a significant improvement in delaying disease progression, suggesting that treatment with chemotherapy can be postponed, preserving the best quality of life possible in these patients for a longer period,” says Joan Carles, Head of Section, Medical Oncology Department at the Vall d’Hebron University Hospital (HUVH), Vall d’Hebron Barcelona Hospital Campus.
“These new additional data from TALAPRO-2 point to the practice-changing potential of this novel combination in the first-line treatment of patients with castration-resistant metastatic prostate cancer harboring homologous recombination repair gene alterations,” concludes Carles.
- Karim Fizazi, Arun Azad, Nobuaki Matsubara, Joan Carles, Andre Fay, Ugo De Giorgi, Jae Young Joung, Peter Fong, Eric Voog, Robert Jones, Neal Shore, Curtis Dunshee, Stefanie Zschaebitz, Jan Oldenburg, Xun Lin, Cynthia Healy, Nicola Di Santo, Fabian Zohren, Neeraj Agarwal. TALAPRO-2: Phase 3 study of talazoparib (TALA) + enzalutamide (ENZA) versus placebo (PBO) + ENZA as first-line (1L) treatment for patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) harboring homologous recombination repair (HRR) gene alterations.