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SAN FRANCISCO – Dual targeting of the androgen signaling axis in metastatic hormone-sensitive prostate cancer improves outcomes and is well tolerated, according to results of the phase 3 ARCHES trial reported at the 2019 Genitourinary Cancers Symposium sponsored by the American Society of Clinical Oncology, ASTRO, and the Society of Urologic Oncology.
“Androgen-deprivation therapy [ADT] has been the mainstay of therapy for men who present with metastatic disease for many years. But generally, progression to castration-resistant diseases is observed within approximately 3 years,” said lead investigator Andrew J. Armstrong, MD, a professor of medicine in medical oncology at Duke University, Durham, N.C.
“Thus the advent of improving outcomes with the [additional] use of early docetaxel, abiraterone, and now radiation to the primary in the face of oligometastatic disease has been shown to improve survival,” he added. “However, the most recent studies have really not studied the sequential use of docetaxel and have largely excluded patients who had had prior docetaxel chemotherapy in the hormone-sensitive setting.”
The investigators in the ARCHES trial (NCT02677896) randomized 1,150 men with metastatic hormone-sensitive prostate cancer to enzalutamide (Xtandi) plus ADT or placebo plus ADT.
With a median follow-up of 14.4 months, radiographic progression-free survival – the trial’s primary endpoint – was prolonged in the enzalutamide arm. Risk of progression or death was reduced by a relative 61% with enzalutamide versus placebo. There were also significant relative reductions in risks of other important outcomes such as time to prostate-specific antigen (PSA) progression (81% reduction), time to new antineoplastic therapy (72% reduction), and time to castration resistance (72% reduction).
Meanwhile, the enzalutamide group had somewhat more fatigue, hot flashes, and hypertension, but most of these events were grade 1 or 2. Rates of adverse events leading to treatment withdrawal were similar and low.
“Following the success of this study, all patients in the placebo group will be offered participation in an open-label extension protocol where they’ll be offered enzalutamide and the opportunity to receive a clinically beneficial treatment,” Dr. Armstrong reported.
Ready for prime time?
The ARCHES findings are probably not yet sufficient to be implemented in real-world practice, according to invited discussant Ian D. Davis, MBBS, PhD, a professor at Monash University, Melbourne.
The condition studied in the trial – metastatic hormone-sensitive prostate cancer – certainly needs treatment, but it is unclear whether radiographic progression-free survival is a meaningful endpoint, he said. “We know in the CRPC [castration-resistant prostate cancer] setting for enzalutamide in the PREVAIL study, radiographic progression-free survival was correlated with overall survival, but we haven’t actually proven that yet in the CSPC [castration-sensitive prostate cancer] setting.”
Toxicity was acceptable, but information about the efficacy of subsequent treatment is lacking. “This is where progression-free survival 2 [PFS2] information would be useful if we had it,” Dr. Davis noted. Cost-effectiveness in terms of overall survival is likewise still unknown.
“Cautiously, and I’m conscious of my conflict of interest here because I’m doing a similar trial, I’d say that the ARCHES trial should probably not yet change practice,” he said. However, he qualified that statement by pointing to recently announced results from the phase 3 TITAN trial (NCT02489318) of apalutamide (Erleada), showing significant radiographic progression-free survival and overall survival benefit in this patient population. “So we await those data with interest.”
The first interim analysis of the enzalutamide trial he is cochairing, ANZUP ENZAMET (NCT02446405), is imminent, according to Dr. Davis. “The differences here are the primary endpoint of ENZAMET is overall survival and there was an early amendment to allow concurrent docetaxel, so a significant proportion of patients on this study will have received concurrent docetaxel with enzalutamide or ADT,” he noted.
Study details
Men enrolled in ARCHES were allowed to have received prior ADT for up to 3 months or, if they had received docetaxel, for up to 6 months, Dr. Armstrong noted at the symposium.
About two-thirds each had high disease volume and had distant metastasis at their initial diagnosis. Overall, median duration of prior ADT was 1.6 months.
Radiographic progression-free survival was not reached with enzalutamide versus 19.45 months with placebo (hazard ratio, 0.39; P less than .0001). Corresponding 12-month rates were 84% and 64%. Findings were essentially the same across diverse subgroups, including among the 18% of patients who had received prior docetaxel (HR, 0.53).
Median time to PSA progression – typically one of the first indications of castration resistance – was not reached in either group, but the 12-month rate was 91% with enzalutamide versus 63% with placebo (HR, 0.19; P less than .0001), Dr. Armstrong reported. Median time to castration resistance was not reached with enzalutamide versus 13.9 months with placebo (HR, 0.28; P less than .0001).
There also were significant differences in favor of enzalutamide on the rate of achievement of undetectable PSA (68.1% vs. 17.6%; P less than .0001), the objective response rate (83.1% vs. 63.7%; P less than .0001), and the time to initiation of new antineoplastic therapy (not reached vs. 30.19 months; HR, 0.28; P less than .0001).
Quality of life was very high in both groups at study baseline and remained similarly so during follow-up. An interim analysis showed overall survival had not been reached in either group, although there was a nonsignificant trend favoring enzalutamide.
Safety was much the same, with the enzalutamide and placebo groups having similar rates of grade 3 or worse adverse events (24.3% vs. 25.6%), as well as similar rates of adverse events leading to treatment withdrawal (7.2% vs. 5.2%) and death (2.4% vs. 1.7%).
In terms of adverse events of special interest, the groups were comparable on rates of grade 3 or 4 convulsion, ischemic heart disease, falls, and fractures.
Dr. Armstrong disclosed that he has a consulting or advisory role with, receives research funding (institutional) from, and receives travel, accommodations, and/or expenses from Astellas – among other disclosures. The trial was sponsored by Astellas.
SOURCE: Armstrong AJ et al. GUCS 2019, Abstract 687.
SAN FRANCISCO – Dual targeting of the androgen signaling axis in metastatic hormone-sensitive prostate cancer improves outcomes and is well tolerated, according to results of the phase 3 ARCHES trial reported at the 2019 Genitourinary Cancers Symposium sponsored by the American Society of Clinical Oncology, ASTRO, and the Society of Urologic Oncology.
“Androgen-deprivation therapy [ADT] has been the mainstay of therapy for men who present with metastatic disease for many years. But generally, progression to castration-resistant diseases is observed within approximately 3 years,” said lead investigator Andrew J. Armstrong, MD, a professor of medicine in medical oncology at Duke University, Durham, N.C.
“Thus the advent of improving outcomes with the [additional] use of early docetaxel, abiraterone, and now radiation to the primary in the face of oligometastatic disease has been shown to improve survival,” he added. “However, the most recent studies have really not studied the sequential use of docetaxel and have largely excluded patients who had had prior docetaxel chemotherapy in the hormone-sensitive setting.”
The investigators in the ARCHES trial (NCT02677896) randomized 1,150 men with metastatic hormone-sensitive prostate cancer to enzalutamide (Xtandi) plus ADT or placebo plus ADT.
With a median follow-up of 14.4 months, radiographic progression-free survival – the trial’s primary endpoint – was prolonged in the enzalutamide arm. Risk of progression or death was reduced by a relative 61% with enzalutamide versus placebo. There were also significant relative reductions in risks of other important outcomes such as time to prostate-specific antigen (PSA) progression (81% reduction), time to new antineoplastic therapy (72% reduction), and time to castration resistance (72% reduction).
Meanwhile, the enzalutamide group had somewhat more fatigue, hot flashes, and hypertension, but most of these events were grade 1 or 2. Rates of adverse events leading to treatment withdrawal were similar and low.
“Following the success of this study, all patients in the placebo group will be offered participation in an open-label extension protocol where they’ll be offered enzalutamide and the opportunity to receive a clinically beneficial treatment,” Dr. Armstrong reported.
Ready for prime time?
The ARCHES findings are probably not yet sufficient to be implemented in real-world practice, according to invited discussant Ian D. Davis, MBBS, PhD, a professor at Monash University, Melbourne.
The condition studied in the trial – metastatic hormone-sensitive prostate cancer – certainly needs treatment, but it is unclear whether radiographic progression-free survival is a meaningful endpoint, he said. “We know in the CRPC [castration-resistant prostate cancer] setting for enzalutamide in the PREVAIL study, radiographic progression-free survival was correlated with overall survival, but we haven’t actually proven that yet in the CSPC [castration-sensitive prostate cancer] setting.”
Toxicity was acceptable, but information about the efficacy of subsequent treatment is lacking. “This is where progression-free survival 2 [PFS2] information would be useful if we had it,” Dr. Davis noted. Cost-effectiveness in terms of overall survival is likewise still unknown.
“Cautiously, and I’m conscious of my conflict of interest here because I’m doing a similar trial, I’d say that the ARCHES trial should probably not yet change practice,” he said. However, he qualified that statement by pointing to recently announced results from the phase 3 TITAN trial (NCT02489318) of apalutamide (Erleada), showing significant radiographic progression-free survival and overall survival benefit in this patient population. “So we await those data with interest.”
The first interim analysis of the enzalutamide trial he is cochairing, ANZUP ENZAMET (NCT02446405), is imminent, according to Dr. Davis. “The differences here are the primary endpoint of ENZAMET is overall survival and there was an early amendment to allow concurrent docetaxel, so a significant proportion of patients on this study will have received concurrent docetaxel with enzalutamide or ADT,” he noted.
Study details
Men enrolled in ARCHES were allowed to have received prior ADT for up to 3 months or, if they had received docetaxel, for up to 6 months, Dr. Armstrong noted at the symposium.
About two-thirds each had high disease volume and had distant metastasis at their initial diagnosis. Overall, median duration of prior ADT was 1.6 months.
Radiographic progression-free survival was not reached with enzalutamide versus 19.45 months with placebo (hazard ratio, 0.39; P less than .0001). Corresponding 12-month rates were 84% and 64%. Findings were essentially the same across diverse subgroups, including among the 18% of patients who had received prior docetaxel (HR, 0.53).
Median time to PSA progression – typically one of the first indications of castration resistance – was not reached in either group, but the 12-month rate was 91% with enzalutamide versus 63% with placebo (HR, 0.19; P less than .0001), Dr. Armstrong reported. Median time to castration resistance was not reached with enzalutamide versus 13.9 months with placebo (HR, 0.28; P less than .0001).
There also were significant differences in favor of enzalutamide on the rate of achievement of undetectable PSA (68.1% vs. 17.6%; P less than .0001), the objective response rate (83.1% vs. 63.7%; P less than .0001), and the time to initiation of new antineoplastic therapy (not reached vs. 30.19 months; HR, 0.28; P less than .0001).
Quality of life was very high in both groups at study baseline and remained similarly so during follow-up. An interim analysis showed overall survival had not been reached in either group, although there was a nonsignificant trend favoring enzalutamide.
Safety was much the same, with the enzalutamide and placebo groups having similar rates of grade 3 or worse adverse events (24.3% vs. 25.6%), as well as similar rates of adverse events leading to treatment withdrawal (7.2% vs. 5.2%) and death (2.4% vs. 1.7%).
In terms of adverse events of special interest, the groups were comparable on rates of grade 3 or 4 convulsion, ischemic heart disease, falls, and fractures.
Dr. Armstrong disclosed that he has a consulting or advisory role with, receives research funding (institutional) from, and receives travel, accommodations, and/or expenses from Astellas – among other disclosures. The trial was sponsored by Astellas.
SOURCE: Armstrong AJ et al. GUCS 2019, Abstract 687.
SAN FRANCISCO – Dual targeting of the androgen signaling axis in metastatic hormone-sensitive prostate cancer improves outcomes and is well tolerated, according to results of the phase 3 ARCHES trial reported at the 2019 Genitourinary Cancers Symposium sponsored by the American Society of Clinical Oncology, ASTRO, and the Society of Urologic Oncology.
“Androgen-deprivation therapy [ADT] has been the mainstay of therapy for men who present with metastatic disease for many years. But generally, progression to castration-resistant diseases is observed within approximately 3 years,” said lead investigator Andrew J. Armstrong, MD, a professor of medicine in medical oncology at Duke University, Durham, N.C.
“Thus the advent of improving outcomes with the [additional] use of early docetaxel, abiraterone, and now radiation to the primary in the face of oligometastatic disease has been shown to improve survival,” he added. “However, the most recent studies have really not studied the sequential use of docetaxel and have largely excluded patients who had had prior docetaxel chemotherapy in the hormone-sensitive setting.”
The investigators in the ARCHES trial (NCT02677896) randomized 1,150 men with metastatic hormone-sensitive prostate cancer to enzalutamide (Xtandi) plus ADT or placebo plus ADT.
With a median follow-up of 14.4 months, radiographic progression-free survival – the trial’s primary endpoint – was prolonged in the enzalutamide arm. Risk of progression or death was reduced by a relative 61% with enzalutamide versus placebo. There were also significant relative reductions in risks of other important outcomes such as time to prostate-specific antigen (PSA) progression (81% reduction), time to new antineoplastic therapy (72% reduction), and time to castration resistance (72% reduction).
Meanwhile, the enzalutamide group had somewhat more fatigue, hot flashes, and hypertension, but most of these events were grade 1 or 2. Rates of adverse events leading to treatment withdrawal were similar and low.
“Following the success of this study, all patients in the placebo group will be offered participation in an open-label extension protocol where they’ll be offered enzalutamide and the opportunity to receive a clinically beneficial treatment,” Dr. Armstrong reported.
Ready for prime time?
The ARCHES findings are probably not yet sufficient to be implemented in real-world practice, according to invited discussant Ian D. Davis, MBBS, PhD, a professor at Monash University, Melbourne.
The condition studied in the trial – metastatic hormone-sensitive prostate cancer – certainly needs treatment, but it is unclear whether radiographic progression-free survival is a meaningful endpoint, he said. “We know in the CRPC [castration-resistant prostate cancer] setting for enzalutamide in the PREVAIL study, radiographic progression-free survival was correlated with overall survival, but we haven’t actually proven that yet in the CSPC [castration-sensitive prostate cancer] setting.”
Toxicity was acceptable, but information about the efficacy of subsequent treatment is lacking. “This is where progression-free survival 2 [PFS2] information would be useful if we had it,” Dr. Davis noted. Cost-effectiveness in terms of overall survival is likewise still unknown.
“Cautiously, and I’m conscious of my conflict of interest here because I’m doing a similar trial, I’d say that the ARCHES trial should probably not yet change practice,” he said. However, he qualified that statement by pointing to recently announced results from the phase 3 TITAN trial (NCT02489318) of apalutamide (Erleada), showing significant radiographic progression-free survival and overall survival benefit in this patient population. “So we await those data with interest.”
The first interim analysis of the enzalutamide trial he is cochairing, ANZUP ENZAMET (NCT02446405), is imminent, according to Dr. Davis. “The differences here are the primary endpoint of ENZAMET is overall survival and there was an early amendment to allow concurrent docetaxel, so a significant proportion of patients on this study will have received concurrent docetaxel with enzalutamide or ADT,” he noted.
Study details
Men enrolled in ARCHES were allowed to have received prior ADT for up to 3 months or, if they had received docetaxel, for up to 6 months, Dr. Armstrong noted at the symposium.
About two-thirds each had high disease volume and had distant metastasis at their initial diagnosis. Overall, median duration of prior ADT was 1.6 months.
Radiographic progression-free survival was not reached with enzalutamide versus 19.45 months with placebo (hazard ratio, 0.39; P less than .0001). Corresponding 12-month rates were 84% and 64%. Findings were essentially the same across diverse subgroups, including among the 18% of patients who had received prior docetaxel (HR, 0.53).
Median time to PSA progression – typically one of the first indications of castration resistance – was not reached in either group, but the 12-month rate was 91% with enzalutamide versus 63% with placebo (HR, 0.19; P less than .0001), Dr. Armstrong reported. Median time to castration resistance was not reached with enzalutamide versus 13.9 months with placebo (HR, 0.28; P less than .0001).
There also were significant differences in favor of enzalutamide on the rate of achievement of undetectable PSA (68.1% vs. 17.6%; P less than .0001), the objective response rate (83.1% vs. 63.7%; P less than .0001), and the time to initiation of new antineoplastic therapy (not reached vs. 30.19 months; HR, 0.28; P less than .0001).
Quality of life was very high in both groups at study baseline and remained similarly so during follow-up. An interim analysis showed overall survival had not been reached in either group, although there was a nonsignificant trend favoring enzalutamide.
Safety was much the same, with the enzalutamide and placebo groups having similar rates of grade 3 or worse adverse events (24.3% vs. 25.6%), as well as similar rates of adverse events leading to treatment withdrawal (7.2% vs. 5.2%) and death (2.4% vs. 1.7%).
In terms of adverse events of special interest, the groups were comparable on rates of grade 3 or 4 convulsion, ischemic heart disease, falls, and fractures.
Dr. Armstrong disclosed that he has a consulting or advisory role with, receives research funding (institutional) from, and receives travel, accommodations, and/or expenses from Astellas – among other disclosures. The trial was sponsored by Astellas.
SOURCE: Armstrong AJ et al. GUCS 2019, Abstract 687.
REPORTING FROM GUCS 2019