ONCAlert | Upfront Therapy for mRCC

Before Starting Targeted Therapy for Prostate Cancer, Determine Cardiovascular Risk

Dylann Cohn-Emery
Published Online: Mar 21,2020
Elderly patients with advanced prostate cancer should be evaluated for preexisting cardiovascular diseases (CVDs) before taking oral androgen signaling inhibitors by a multidisciplinary team, includ­ing a cardiologist, according to a recent retro­spective study. Investigators at Thomas Jeffer­son University in Philadelphia, Pennsylvania, demonstrated that after receiving abiraterone acetate (Zytiga) or enzalutamide (Xtandi), these patients had higher rates of short-term mortality than similar patients without CVDs.1

“Once clinical trials demonstrate the efficacy of a drug in a selective group of patients, the next step is to study whether the drug is effective in the population excluded from the pivotal trials,” lead author Grace Lu-Yao, PhD, MPH, associate director of population science at the Sidney

Kimmel Cancer Center—Jefferson Health, wrote in an email interview with Targeted Therapies in Oncology.

“It is common that patients not eligible for the pivotal trials receive the approved drugs,” she continued. “The benefits observed in clini­cal trials may not apply to patients who do not meet the trial eligibility criteria. In fact, it has been shown that the net risks may outweigh the benefits for patients treated with androgen-deprivation therapy [ADT] if they have signifi­cant preexisting conditions.”

In the population-based study, patients with pre-existing significant cardiovascular condi­tions treated with abiraterone or enzalutamide after docetaxel showed a higher 6-month mor­tality rate compared with pivotal clinical trials results, such as those recorded in COU-AA-301 (NCT00638690) and AFFIRM (NCT00974311). When patients were not given docetaxel before being treated with abiraterone or enzalutamide, they had a higher 6-month crude mortality rate if they also had preexisting CVDs versus patients without them. The mortality rates post chemotherapy and without chemotherapy can be seen in FIGURE 1.1

Whether or not docetaxel was used, ≥3 CVD diagnoses were associated with a higher 6-month mortality relative risk compared with patients without CVDs after abiraterone or enzalut­amide (adjusted relative risk 1.43 for patients treated with docetaxel previously and 1.56 for patients without docetaxel). Most of the survival differences between patients with CVD diagno­ses and patients without CVD diagnoses occurred in the first 6 months of initial treatment with abiraterone or enzalutamide.

“The benefits of the androgen signaling inhibi­tors might not be applicable to patients who have a history of significant [CVDs],” Lu-Yao said. “For patients who do not meet the trial eligibility cri­teria, risk assessment of potential CVD adverse effect and shared decision making is essential. Pretreatment rehabilitation might be needed before the patients start the medication.”

Abiraterone was linked to higher hospitaliza­tion rates irrespective of preexisting CVDs in patients who did not receive docetaxel, based on the adjusted incidence rate ratios (IRRs). It was also associated with a significant increase in posttreatment hospitalization in patients on various classes of medications. Hospitalization rates between abiraterone and enzalutamide showed no significant differences in the post-chemotherapy group, but patients with 1 or 2 CVD diagnoses had a 43% higher risk rate of hospitalization versus patients with no CVDs (adjusted IRR, 1.43; 95% CI, 1.15-1.78), as shown in FIGURE 2.1

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Before Starting Targeted Therapy for Prostate Cancer, Determine Cardiovascular Risk
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