Research frontiers Safety outcomes of the TALAPRO-1 study

 The TALAPRO-1 study (NCT03148795) is an international phase II trial evaluating the efficacy and tolerability of talazoparib monotherapy in patients with metastatic castration-resistant prostate cancer (mCRPC) and DDR-HRR gene mutations.

Talazoparib is a novel polyADP ribose polymerase (PARP) inhibitor, and this article analyzes the safety data of Talazoparib in mCRPC patients in detail, which may provide some insights
for clinicians to manage adverse events (AEs) and conduct clinical trials of Talazoparib in combination with other anticancer drugs.

Patients were given oral Talazoparib 1.
0 mg/day (0.
75 mg/day in patients with moderate renal impairment) until imaging progression, intolerable toxicity, dropout, or death
.
Safety outcomes included incidence, severity, time of occurrence, duration, overlap of adverse events (TEAEs) occurring during treatment (simultaneous experience of two AEs≥1 day), dose adjustment/discontinuation due to AEs, and significant changes
in laboratory indicators and vital signs.

Among the safety population (N = 127, median age 69 years), 95.
3% (121/127) of patients experienced TEAEs
.
The most common TEAEs were anaemia (62/127; 48.
8%), nausea and vomiting (42/127; 33.
1%), loss of appetite (36/127; 28.
3%), and fatigue (30/127; 23.
6%)
.
Non-hematology TEAEs are usually grade
1 and 2.
No grade 5 TEAEs or treatment-related deaths
occurred.

Fig.
1 Levels of TEAEs occurring in the safety population (A: Comprehensive; B: Hematology TEAEs; C: Non-hematology TEAEs)

Hematology TEAEs usually occur in the 4-5 months of treatment start, the median duration of grade 3/4 hematology TEAEs such as anemia, neutropenia, and thrombocytopenia is usually 7-12 days, and patients do not experience grade 4 anemia or neutropenia events
.
BRCA status and source of mutations in the DDR-HRR gene were not significantly associated
with patient safety outcomes.
The median duration of treatment for patients treated with Talazoparib was 6.
1 (range: 0.
4-24.
9) months, independent
of the incidence of anaemia.
Of the 15 (15/127; 11.
8%) patients with permanent treatment interruption due to AEs, only 3 were discontinued due to hematology TEAEs, of which 2 (2/127; 1.
6%) had thrombocytopenia and 1 (1/127; 0.
8%) leukopenia
.

In the TALAPRO-1 study, no new safety signals
were observed with Talazoparib monotherapy.
Clinicians can address common TEAEs associated with Talazoparib with dose titrations and supportive care, and the controlled safety profile and good antitumor activity support future Phase III trials to further evaluate the use
of Talazoparib in mCRPC.

References:

Mehra N, Fizazi K, de Bono JS, et al.
Talazoparib, a Poly(ADP-ribose) Polymerase Inhibitor, for Metastatic Castration-resistant Prostate Cancer and DNA Damage Response Alterations: TALAPRO-1 Safety Analyses.
Oncologist.
2022 Oct 1; 27(10):e783-e795.