Serbas L

Purpose: To determine which sequence of abiraterone (ABI) and enzalutamide (ENZA) shows better survival outcomes in Veterans diagnosed with metastatic castration-resistant prostate cancer (mCRPC) at VA San Diego.

Background: Prostate cancer is the leading cancer diagnosis among American men who eventually develop mCRPC. Therapies for mCRPC include androgen receptor pathway inhibitors like ABI and ENZA. Both improve survival independently; however, the optimal treatment sequence has not been determined. Retrospective studies have shown that the ABI-ENZA sequence significantly improves progression-free survival (PFS) and combined prostate-specific antigen PFS (cPSA-PFS), but not overall survival (OS).

Methods: A retrospective chart review was conducted in subjects with mCRPC who had received ABI and ENZA sequentially in either order. Subjects must have received at least one month of each drug; those who had an interruption of treatment sequence were excluded. The primary outcomes were to compare cPSA-PFS and OS between the two sequences; cPSA-PFS represented time from start of drug 1 to > 25% PSA increase from baseline/nadir on drug 2, while OS represented time from start of drug 1 to death from any cause. OS and cPSA-PFS were reported via Kaplan-
Meier curves and hazard ratios (HR). Ninety-eight subjects per group were needed to reach 80% power for an effect size of 0.404 in cPSA-PFS.

Results: Forty subjects were identified and 8 were excluded; of the remaining, 9 received ENZA-ABI and 23 received ABIENZA. Baseline characteristics were similar. There were no differences in cPSA-PFS between ENZA-ABI and ABI-ENZA: median 406 days versus 534 days (HR 1.39, 95% CI 0.59-1.53, P = .59), respectively. OS did not differ between ENZAABI and ABI-ENZA: median 711 days versus 803 days (HR 0.88, 95% CI 0.35-1.59, P = .21), respectively.

Conclusions: There were no significant differences in outcomes between sequences although ABI-ENZA showed longer cPSA-PFS and OS. This is consistent with previous studies where ABI-ENZA had significantly longer PFS and cPSA-PFS; ABI-ENZA OS was longer but not significantly different in those studies. Limitations included a small sample size and uneven groups. Ultimately, ABI-ENZA should be considered as the sequence-of-choice for treatment of mCRPC until prospective studies confirm the optimal sequence.

Purpose: To determine which sequence of abiraterone (ABI) and enzalutamide (ENZA) shows better survival outcomes in Veterans diagnosed with metastatic castration-resistant prostate cancer (mCRPC) at VA San Diego.

Background: Prostate cancer is the leading cancer diagnosis among American men who eventually develop mCRPC. Therapies for mCRPC include androgen receptor pathway inhibitors like ABI and ENZA. Both improve survival independently; however, the optimal treatment sequence has not been determined. Retrospective studies have shown that the ABI-ENZA sequence significantly improves progression-free survival (PFS) and combined prostate-specific antigen PFS (cPSA-PFS), but not overall survival (OS).

Methods: A retrospective chart review was conducted in subjects with mCRPC who had received ABI and ENZA sequentially in either order. Subjects must have received at least one month of each drug; those who had an interruption of treatment sequence were excluded. The primary outcomes were to compare cPSA-PFS and OS between the two sequences; cPSA-PFS represented time from start of drug 1 to > 25% PSA increase from baseline/nadir on drug 2, while OS represented time from start of drug 1 to death from any cause. OS and cPSA-PFS were reported via Kaplan-
Meier curves and hazard ratios (HR). Ninety-eight subjects per group were needed to reach 80% power for an effect size of 0.404 in cPSA-PFS.

Results: Forty subjects were identified and 8 were excluded; of the remaining, 9 received ENZA-ABI and 23 received ABIENZA. Baseline characteristics were similar. There were no differences in cPSA-PFS between ENZA-ABI and ABI-ENZA: median 406 days versus 534 days (HR 1.39, 95% CI 0.59-1.53, P = .59), respectively. OS did not differ between ENZAABI and ABI-ENZA: median 711 days versus 803 days (HR 0.88, 95% CI 0.35-1.59, P = .21), respectively.

Conclusions: There were no significant differences in outcomes between sequences although ABI-ENZA showed longer cPSA-PFS and OS. This is consistent with previous studies where ABI-ENZA had significantly longer PFS and cPSA-PFS; ABI-ENZA OS was longer but not significantly different in those studies. Limitations included a small sample size and uneven groups. Ultimately, ABI-ENZA should be considered as the sequence-of-choice for treatment of mCRPC until prospective studies confirm the optimal sequence.

Purpose: To determine which sequence of abiraterone (ABI) and enzalutamide (ENZA) shows better survival outcomes in Veterans diagnosed with metastatic castration-resistant prostate cancer (mCRPC) at VA San Diego.

Background: Prostate cancer is the leading cancer diagnosis among American men who eventually develop mCRPC. Therapies for mCRPC include androgen receptor pathway inhibitors like ABI and ENZA. Both improve survival independently; however, the optimal treatment sequence has not been determined. Retrospective studies have shown that the ABI-ENZA sequence significantly improves progression-free survival (PFS) and combined prostate-specific antigen PFS (cPSA-PFS), but not overall survival (OS).

Methods: A retrospective chart review was conducted in subjects with mCRPC who had received ABI and ENZA sequentially in either order. Subjects must have received at least one month of each drug; those who had an interruption of treatment sequence were excluded. The primary outcomes were to compare cPSA-PFS and OS between the two sequences; cPSA-PFS represented time from start of drug 1 to > 25% PSA increase from baseline/nadir on drug 2, while OS represented time from start of drug 1 to death from any cause. OS and cPSA-PFS were reported via Kaplan-
Meier curves and hazard ratios (HR). Ninety-eight subjects per group were needed to reach 80% power for an effect size of 0.404 in cPSA-PFS.

Results: Forty subjects were identified and 8 were excluded; of the remaining, 9 received ENZA-ABI and 23 received ABIENZA. Baseline characteristics were similar. There were no differences in cPSA-PFS between ENZA-ABI and ABI-ENZA: median 406 days versus 534 days (HR 1.39, 95% CI 0.59-1.53, P = .59), respectively. OS did not differ between ENZAABI and ABI-ENZA: median 711 days versus 803 days (HR 0.88, 95% CI 0.35-1.59, P = .21), respectively.

Conclusions: There were no significant differences in outcomes between sequences although ABI-ENZA showed longer cPSA-PFS and OS. This is consistent with previous studies where ABI-ENZA had significantly longer PFS and cPSA-PFS; ABI-ENZA OS was longer but not significantly different in those studies. Limitations included a small sample size and uneven groups. Ultimately, ABI-ENZA should be considered as the sequence-of-choice for treatment of mCRPC until prospective studies confirm the optimal sequence.

Purpose: The purpose of this study was to characterize the incidence of cardiovascular events and time to first cardiovascular event due to tyrosine kinase inhibitors (TKIs) in patients with advanced RCC at VASDHS. Additional aims were to describe the current clinical practice management of cardiac monitoring via EKG or ECHO in this patient population.

Background: Over the past 12 years, the US Food and Drug Administration has approved six multitargeted TKIs for the treatment of RCC: axitinib, cabozantinib, lenvatinib, pazopanib, sorafenib and sunitinib. Other than hypertension, most studies of these therapies did not report the incidence of cardiovascular events that occurred during early clinical trials.

Methodology: This was a retrospective study that evaluated the incidence of cardiovascular events in patients diagnosed with advanced RCC who received oral TKI therapy for at least 30 days. The incidence of cardiovascular events was collected in accordance with the Common Terminology Criteria for Adverse Events (CTCAE) grading at predetermined time points from the start of each TKI therapy. Cardiovascular events were defined as hypertension, QT prolongation, congestive heart failure (CHF), stroke, myocardial infarction (MI) and pulmonary hypertension.

Results: Fifty-four patients were included in this study with a median age of 66 years. There were no cardiac events in patients without a history of cardiovascular disease. Eleven patients with a history of cardiovascular disease experienced an adverse cardiac event while taking pazopanib, sorafenib, or sunitinib. The most common adverse events were hypertension (n=6) and MI (n=2). The remaining three patients experienced a stroke, QT prolongation, or CHF. Seventy-three percent of events occurred within four months of starting therapy. Baseline EKG or ECHO were not available for most patients started on TKI therapy and obtained only when patients were symptomatic.

Conclusions: The results of this study indicate a need for baseline and routine monitoring in patients started on oral TKIs with a history of cardiovascular disease to align with the current recommendations as listed in the medication package inserts. Based on the results of this study, baseline and routine monitoring should be considered during the first four months of therapy in patients with a history of cardiovascular disease.

Purpose: The purpose of this study was to characterize the incidence of cardiovascular events and time to first cardiovascular event due to tyrosine kinase inhibitors (TKIs) in patients with advanced RCC at VASDHS. Additional aims were to describe the current clinical practice management of cardiac monitoring via EKG or ECHO in this patient population.

Background: Over the past 12 years, the US Food and Drug Administration has approved six multitargeted TKIs for the treatment of RCC: axitinib, cabozantinib, lenvatinib, pazopanib, sorafenib and sunitinib. Other than hypertension, most studies of these therapies did not report the incidence of cardiovascular events that occurred during early clinical trials.

Methodology: This was a retrospective study that evaluated the incidence of cardiovascular events in patients diagnosed with advanced RCC who received oral TKI therapy for at least 30 days. The incidence of cardiovascular events was collected in accordance with the Common Terminology Criteria for Adverse Events (CTCAE) grading at predetermined time points from the start of each TKI therapy. Cardiovascular events were defined as hypertension, QT prolongation, congestive heart failure (CHF), stroke, myocardial infarction (MI) and pulmonary hypertension.

Results: Fifty-four patients were included in this study with a median age of 66 years. There were no cardiac events in patients without a history of cardiovascular disease. Eleven patients with a history of cardiovascular disease experienced an adverse cardiac event while taking pazopanib, sorafenib, or sunitinib. The most common adverse events were hypertension (n=6) and MI (n=2). The remaining three patients experienced a stroke, QT prolongation, or CHF. Seventy-three percent of events occurred within four months of starting therapy. Baseline EKG or ECHO were not available for most patients started on TKI therapy and obtained only when patients were symptomatic.

Conclusions: The results of this study indicate a need for baseline and routine monitoring in patients started on oral TKIs with a history of cardiovascular disease to align with the current recommendations as listed in the medication package inserts. Based on the results of this study, baseline and routine monitoring should be considered during the first four months of therapy in patients with a history of cardiovascular disease.

Purpose: The purpose of this study was to characterize the incidence of cardiovascular events and time to first cardiovascular event due to tyrosine kinase inhibitors (TKIs) in patients with advanced RCC at VASDHS. Additional aims were to describe the current clinical practice management of cardiac monitoring via EKG or ECHO in this patient population.

Background: Over the past 12 years, the US Food and Drug Administration has approved six multitargeted TKIs for the treatment of RCC: axitinib, cabozantinib, lenvatinib, pazopanib, sorafenib and sunitinib. Other than hypertension, most studies of these therapies did not report the incidence of cardiovascular events that occurred during early clinical trials.

Methodology: This was a retrospective study that evaluated the incidence of cardiovascular events in patients diagnosed with advanced RCC who received oral TKI therapy for at least 30 days. The incidence of cardiovascular events was collected in accordance with the Common Terminology Criteria for Adverse Events (CTCAE) grading at predetermined time points from the start of each TKI therapy. Cardiovascular events were defined as hypertension, QT prolongation, congestive heart failure (CHF), stroke, myocardial infarction (MI) and pulmonary hypertension.

Results: Fifty-four patients were included in this study with a median age of 66 years. There were no cardiac events in patients without a history of cardiovascular disease. Eleven patients with a history of cardiovascular disease experienced an adverse cardiac event while taking pazopanib, sorafenib, or sunitinib. The most common adverse events were hypertension (n=6) and MI (n=2). The remaining three patients experienced a stroke, QT prolongation, or CHF. Seventy-three percent of events occurred within four months of starting therapy. Baseline EKG or ECHO were not available for most patients started on TKI therapy and obtained only when patients were symptomatic.

Conclusions: The results of this study indicate a need for baseline and routine monitoring in patients started on oral TKIs with a history of cardiovascular disease to align with the current recommendations as listed in the medication package inserts. Based on the results of this study, baseline and routine monitoring should be considered during the first four months of therapy in patients with a history of cardiovascular disease.