Side effects such as anemia and other blood-related events were resolved with dose reductions and/or supportive care in men with metastatic castration-resistant prostate cancer.
Side effects resulting from treatment with Talzenna (talazoparib) plus Xtandi (enzalutamide) in men with metastatic castration-resistant prostate cancer were generally manageable with dosing changes or supportive care, according to safety results from a recent study.
Findings from the phase 3 TALAPRO-2 study were presented during the 2023 ASCO Annual Meeting in Chicago.
“TALAPRO-2 is the first phase 3 study to evaluate (Talzenna) plus (Xtandi) as a first-line treatment in patients with metastatic castration resistant prostate cancer,” said Dr. Arun Azad, medical oncologist at Peter MacCallum Cancer Centre in Australia, during a presentation of the results. “Here we provide a detailed overview of the safety profile of (Talzenna) plus (Xtandi) in the all-comers population of the TALAPRO-2 trial, with the aim of understanding how (side effects) were managed.”
Patients in the phase 3 TALAPRO-2 study were randomly assigned Talzenna or placebo plus Xtandi. A total of 398 patients were included, which included patients with homologous recombination repair gene alterations. According to the National Cancer Institute, changes in the homologous recombination repair pathway can lead to the inability to repair DNA and potentially diseases like cancer.
Data showed that 98.5% of patients experienced all-cause any-grade treatment-emergent side effects. Serious treatment-emergent side effects were experienced in 19.6% of patients, and 19.1% discontinued treatment with Talzenna due to these side effects. The rate of discontinuation of placebo due to treatment-emergent side effects in the placebo/Xtandi cohort was 12.2%.
The most common severe or life-threatening treatment-emergent side effect in the Talzenna/Xtandi arm was anemia (65.8%), which led to a discontinuation of treatment in 8.3% of patients. The median time to first onset of severe or worse anemia in patients was 3.3 months, and the median duration was 16 days. Anemia was managed in patients using dose modification once anemia was severe or worse, and/or with standard supportive care. Among all patients, 43.2% received dose reduction due to anemia.
“Despite dose reduction, the relative dose intensity of (Talzenna) remained high, above 80%. The incidence of (Talzenna) dose interruptions and reductions was similar during the all-comers and (homologous recombination repair) deficient only populations. However, the rate of (Talzenna) discontinuation due to (side effects) was about half in the (homologous recombination repair) deficient cohort compared to the all-comers cohort,” said Azad.
Other common blood-related treatment-emergent side effects in the all-comers cohort included neutropenia (low number of neutrophils, a type of white blood cell), which was observed in 35.7% of patients, and thrombocytopenia (lower than normal number of platelets in blood that can lead to easy bruising and excessing bleeding), which was observed in 24.6% of patients. Median onset of neutropenia was 2.3 months, and median duration was 12 days. Median onset of thrombocytopenia was 2.3 months, and median duration was 19 days.
The three most common non-hematologic treatment emergent side effects included fatigue (33.7%), back pain (22.1%) and decreased appetite (21.6%).
Overall, the median treatment duration of Talzenna was 19.8 months. Severe or worse treatment-emergent side effects typically occurred early in treatment (within six months of starting treatment) and resolved in less than a month with dose modification and supportive care.
Similar incidence of all-cause treatment-emergent side effects was seen between the all-comers cohort and the homologous recombination repair deficient only cohort.
TALAPRO-2 is an ongoing phase 3 study ofTalzenna plus Xtandi in patients with metastatic castration-resistant prostate cancer. Patients were divided into two groups, made up of those with and without homologous recombination repair gene alterations (all-comers) and a homologous recombination repair -deficient only cohort.
The trial recently reported a clinically meaningful and statistically significant improvement in radiographic progression-free survival (the time during and after treatment when a patient with cancer is alive without disease worsening, as confirmed through radiography) among patients receiving Talzenna plus Xtandi versus placebo plus Xtandi, regardless of homologous recombination repair status.
At the time of data presentation, the median radiographic progression-free survival had not yet been met for patients receiving Talzenna and Xtandi, compared with 21.9 months among those receiving placebo plus Xtandi. Overall, the addition of Talzenna was found to reduce the risk of progression or death by 37%.
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