Pairing talazoparib with enzalutamide may be significantly more effective than enzalutamide alone, especially for HRR-positive patients.
Treating metastatic castration-resistant prostate cancer (mCRPC) with talazoparib on top of the standard first-line treatment led to a 37% reduction in the risk of radiographic progression or death, new data shows.
TALAPRO-2 was a randomised, double-blind, placebo-controlled, phase three trial of 803 men with mCRPC who had not yet received chemotherapy or novel hormonal therapy.
The half in the treatment group received enzalutamide, the androgen receptor inhibitor that has been widely used as the standard therapy for mCRPC, combined with talazoparib, while the control group received enzalutamide alongside a placebo.
The median radiographic progression-free survival (rPFS) was 16.4 months in the control group, and 27.9 months in the treatment group.
Researchers found that this improvement in rPFS was even more pronounced amongst those who were genetically homologous recombination repair (HRR) positive.
More than 50% of patients in this group were still progression-free at the time of data cutoff so a median rPFS could not be determined. However, by this time, the placebo group had a median rPFS of 13.8 months, meaning half the patients had already progressed or died by that time.
Nearly half of the total participants were HRR-positive and were spread evenly across the control group and the treatment group.
Secondary outcomes included PSA progression, which was significantly delayed in the treatment group compared with the control group, suggesting better early disease control. Patients receiving the combined therapy experienced a 61% reduction in the risk of PSA progression.
Roughly 20% of the cohort had measurable soft tissue disease and were evaluated for an objective response rate (ORR). In the treatment group, 61% of these patients achieved a partial or complete response to treatment and had tumours which shrank significantly by RECIST (Response Evaluation Criteria In Solid Tumours) standards. In the control group, this proportion was 43%, indicating deeper tumour responses in measurable disease when PARP inhibition is included as part of first-line treatment.
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The main side effect was grade three or four anaemia, occurring in nearly half of all participants in the treatment group. Thrombocytopenia was reported in 8% of the treatment group, and 15% experienced neutropenia, compared with less than 1% of patients in the control group experiencing either of these events
These hematologic toxicities triggered a dose reduction by researchers in nearly 50% of the treatment group. However, discontinuation due to adverse events only occurred in 19% of the treatment group, compared to12% of the control group.
The study concluded that combining talazopirab with enzalutamide significantly prolonged radiographic progression-free survival, particularly in men with HRR gene mutations. However, hematologic toxicity management will be crucial in clinical practice.
