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A central aim of prostate cancer treatment is to prolong survival, but trials often overlook another key goal: Improving — or at least maintaining — quality of life (QoL).
The trials explored the effects of treatment suspension or intensification on health-related QoL as well as interventions to manage side effects in different patient populations.
The first presentation focused on a post hoc analysis of the phase 3 EMBARK trial, which looked at the effect of suspending treatment on health-related QoL in men with nonmetastatic disease at a high risk for biochemical recurrence.
Earlier findings from the trial, presented at ESMO in 2023, showed enzalutamide alone or in combination with androgen deprivation therapy (ADT) was associated with a significant improvement in metastasis-free survival vs placebo plus leuprolide.
The initial trial randomized 1068 patients at a high risk for biochemical recurrence to these three treatment groups and suspended therapy at week 37 if prostate-specific antigen (PSA) levels fell below 0.2 ng/mL. Patients, however, were not randomized into the treatment suspension groups. Treatment resumed if PSA levels rose to ≥ 2.0 ng/mL in patients who had undergone radical prostatectomy or ≥ 5.0 ng/mL in those who had not had surgery.
The post hoc analysis, which assessed patient-reported QoL outcomes following treatment suspension at baseline and every 12 weeks until progression, found no meaningful changes in the worst pain in the past 24 hours, as measured by the Brief Pain Inventory–Short Form.
Patients also reported no meaningful changes in total and physical well-being scores on the Functional Assessment of Cancer Therapy–Prostate (FACT-P) and on the European Quality of Life Five-Dimensions (EuroQol-5D) visual analog scale score, as well as no meaningful changes in sexual activity and urinary and bowel symptoms, based on scores from the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire–Prostate 25 (QLQ-PR25).
Hormone treatment-related symptoms on the QLQ-PR25, however, “quickly improved but eventually began to worsen after week 97,” explained lead author Stephen J. Freedland, MD, from Cedars-Sinai Medical Center, Los Angeles, California, who presented the new findings at ASCO.
Dr. Freedland concluded that the EMBARK results show that enzalutamide, with or without ADT, improves metastasis-free survival vs leuprolide alone, without affecting global health-related QoL during treatment or after treatment suspension.
However, Channing J. Paller, MD, of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Medicine, Baltimore, Maryland, who was not involved in the research, pointed out that “patient selection is key” when choosing therapies, given that ADT has distinct adverse effects. Comorbidities and adverse effects “must be taken into consideration to help the doctor and patient make more personalized treatment choices.”
Treatment Intensification and QoL
Another presentation explored health-related QoL outcomes from the phase 3 PRESTO trial.
The study examined ADT intensification in 504 patients who had high-risk biochemically relapsed nonmetastatic hormone-sensitive prostate cancer and a PSA doubling time of 9 months or less. Patients were randomized to ADT monotherapy with degarelix or leuprolide, ADT plus apalutamide, or ADT plus apalutamide, abiraterone acetate, and prednisone.
In previous data from PRESTO, the combination therapy groups both had significantly longer median PSA progression-free survival than the ADT monotherapy arm.
The latest data looked at the health-related QoL outcomes in the PRESTO population, measured using the Expanded Prostate Cancer Index Composite, the PROMIS Fatigue tool, the Hot Flash Related Daily Interference Scale, and the EuroQol-5D.
Ronald C. Chen, MD, MPH, of the University of Kansas Medical Center, Kansas City, who presented the new findings at ASCO, reported that ADT plus apalutamide improved PSA progression-free survival over ADT alone and did not meaningfully increase common treatment-related symptoms, such as hormonal symptoms, sexual dysfunction, hot flash interference, and fatigue.
However, treatment intensification with triple androgen regimen did not lead to further improvements in PSA progression-free survival but did increase the rate of serious adverse events, the time to testosterone recover, and increased hot flash interference.
PRESTO as well as EMBARK “provide a strong rationale for intensification of androgen blockade in men with high-risk biochemical recurrence after completing primary local therapy” and could even “reduce the need for subsequent treatment,” concluded Dr. Chen.
CBT for Managing ADT Side Effects
Up to 80% of men receiving ADT to treat prostate cancer experience night sweats and hot flashes, which are associated with sleep disturbance, anxiety, low mood, and cognitive impairments.
A third trial presented during the session looked at the impact of cognitive-behavioral therapy (CBT) on these side effects of ADT treatment.
Initial findings from the MANCAN study found that CBT delivered by a psychologist reduced the impact of hot flashes and night sweats at 6 weeks.
The MANCAN2 study assessed QoL at 6 months among 162 patients with localized or advanced prostate cancer who underwent at least 6 months of continuous ADT and who experienced more severe hot flashes and night sweats, defined as a score of ≥ 2 on the hot flashes and night sweats problem rating scale.
Study participants were randomized to CBT plus treatment as usual, or treatment as usual alone, with the intervention consisting of two CBT group sessions 4 weeks apart. Between CBT sessions, patients could refer to a booklet and CD, alongside exercises and CBT strategies.
MANCAN2 confirmed that CBT was associated with a significantly greater reduction in hot flash and night sweat scores over standard care alone at 6 weeks. Patients receiving CBT also reported better QoL, sleep, and functional status but those differences did not reach statistical significance.
By 6 months, those in the CBT group still reported better outcomes in each category, but no differences were statistically significant at this time point. Overall, however, 14% of treatment as usual alone patients discontinued ADT at 6 months vs none in the CBT arm.
“Further research is therefore needed to determine whether or not you can make this effect more durable” and to look at “the potential for CBT to support treatment compliance,” said study presenter Simon J. Crabb, PhD, MBBS, from the University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, England.
QoL With Radioligand Crossover
Finally, the phase 3 PSMAfore study compared 177Lu-PSMA-617 with abiraterone or enzalutamide in 468 taxane-naive patients with metastatic castration-resistant prostate cancer who had progressed on a previous androgen receptor pathway inhibitor.
In earlier analyses, Karim Fizazi, MD, PhD, Institut Gustave Roussy, Université Paris-Saclay, Paris, France, reported that 177Lu-PSMA-617 improved radiographic progression-free survival by 59% over androgen receptor pathway inhibitor therapy but did not lead to significant differences in overall survival.
In a new interim analysis, Dr. Fizazi and colleagues explored outcomes in patients eligible to cross over to 177Lu-PSMA-617 following androgen receptor pathway inhibitor therapy. Assessments of health-related QoL revealed that 177Lu-PSMA-617 led to about a 40% improvement in scores on two QoL tools — 41% with FACT-P and 39% with EuroQol-5D.
On subscales of FACT-P, Dr. Fizazi reported that 177Lu-PSMA-617 was also associated with a significantly longer time to worsening in physical, functional, and emotional well-being over standard therapy. A pain inventory score indicated that 177Lu-PSMA-617 led to a 31% improvement in the time to worsening pain intensity, as well as a 33% increase in the time to worsening pain interference.
With the treatment having a “favorable safety profile,” Dr. Fizazi said the results suggest 177Lu-PSMA-617 is a “treatment option” for patients with metastatic castration-resistant prostate cancer who have undergone androgen receptor pathway inhibitor treatment.
MANCAN2 was funded by the UK National Institute for Health and Care Research. EMBARK was funded by Astellas Pharma and Pfizer, the codevelopers of enzalutamide. PRESTO was funded by Alliance Foundation Trials and Johnson & Johnson. PSMAfore was funded by Novartis. Dr. Freedland declared relationships with Pfizer and Astellas Pharma, among others. Paller declared relationships with AstraZeneca, Dendreon, Exelixis, Janssen Oncology, Omnitura, Lilly, and Bayer. Dr. Chen declared relationships with Astellas Pharma, Pfizer, and others. Dr. Crabb declared relationships with AstraZeneca, Bristol-Myers Squibb, Ipsen, Merck, Amgen, Amphista Therapeutics, Bayer, Janssen, MSD, Pfizer, Astex Pharmaceuticals, Clovis Oncology, and Roche. Dr. Fizazi reported relationships with Novartis, AstraZeneca, and a dozen other companies.
A version of this article first appeared on Medscape.com.
A central aim of prostate cancer treatment is to prolong survival, but trials often overlook another key goal: Improving — or at least maintaining — quality of life (QoL).
The trials explored the effects of treatment suspension or intensification on health-related QoL as well as interventions to manage side effects in different patient populations.
The first presentation focused on a post hoc analysis of the phase 3 EMBARK trial, which looked at the effect of suspending treatment on health-related QoL in men with nonmetastatic disease at a high risk for biochemical recurrence.
Earlier findings from the trial, presented at ESMO in 2023, showed enzalutamide alone or in combination with androgen deprivation therapy (ADT) was associated with a significant improvement in metastasis-free survival vs placebo plus leuprolide.
The initial trial randomized 1068 patients at a high risk for biochemical recurrence to these three treatment groups and suspended therapy at week 37 if prostate-specific antigen (PSA) levels fell below 0.2 ng/mL. Patients, however, were not randomized into the treatment suspension groups. Treatment resumed if PSA levels rose to ≥ 2.0 ng/mL in patients who had undergone radical prostatectomy or ≥ 5.0 ng/mL in those who had not had surgery.
The post hoc analysis, which assessed patient-reported QoL outcomes following treatment suspension at baseline and every 12 weeks until progression, found no meaningful changes in the worst pain in the past 24 hours, as measured by the Brief Pain Inventory–Short Form.
Patients also reported no meaningful changes in total and physical well-being scores on the Functional Assessment of Cancer Therapy–Prostate (FACT-P) and on the European Quality of Life Five-Dimensions (EuroQol-5D) visual analog scale score, as well as no meaningful changes in sexual activity and urinary and bowel symptoms, based on scores from the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire–Prostate 25 (QLQ-PR25).
Hormone treatment-related symptoms on the QLQ-PR25, however, “quickly improved but eventually began to worsen after week 97,” explained lead author Stephen J. Freedland, MD, from Cedars-Sinai Medical Center, Los Angeles, California, who presented the new findings at ASCO.
Dr. Freedland concluded that the EMBARK results show that enzalutamide, with or without ADT, improves metastasis-free survival vs leuprolide alone, without affecting global health-related QoL during treatment or after treatment suspension.
However, Channing J. Paller, MD, of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Medicine, Baltimore, Maryland, who was not involved in the research, pointed out that “patient selection is key” when choosing therapies, given that ADT has distinct adverse effects. Comorbidities and adverse effects “must be taken into consideration to help the doctor and patient make more personalized treatment choices.”
Treatment Intensification and QoL
Another presentation explored health-related QoL outcomes from the phase 3 PRESTO trial.
The study examined ADT intensification in 504 patients who had high-risk biochemically relapsed nonmetastatic hormone-sensitive prostate cancer and a PSA doubling time of 9 months or less. Patients were randomized to ADT monotherapy with degarelix or leuprolide, ADT plus apalutamide, or ADT plus apalutamide, abiraterone acetate, and prednisone.
In previous data from PRESTO, the combination therapy groups both had significantly longer median PSA progression-free survival than the ADT monotherapy arm.
The latest data looked at the health-related QoL outcomes in the PRESTO population, measured using the Expanded Prostate Cancer Index Composite, the PROMIS Fatigue tool, the Hot Flash Related Daily Interference Scale, and the EuroQol-5D.
Ronald C. Chen, MD, MPH, of the University of Kansas Medical Center, Kansas City, who presented the new findings at ASCO, reported that ADT plus apalutamide improved PSA progression-free survival over ADT alone and did not meaningfully increase common treatment-related symptoms, such as hormonal symptoms, sexual dysfunction, hot flash interference, and fatigue.
However, treatment intensification with triple androgen regimen did not lead to further improvements in PSA progression-free survival but did increase the rate of serious adverse events, the time to testosterone recover, and increased hot flash interference.
PRESTO as well as EMBARK “provide a strong rationale for intensification of androgen blockade in men with high-risk biochemical recurrence after completing primary local therapy” and could even “reduce the need for subsequent treatment,” concluded Dr. Chen.
CBT for Managing ADT Side Effects
Up to 80% of men receiving ADT to treat prostate cancer experience night sweats and hot flashes, which are associated with sleep disturbance, anxiety, low mood, and cognitive impairments.
A third trial presented during the session looked at the impact of cognitive-behavioral therapy (CBT) on these side effects of ADT treatment.
Initial findings from the MANCAN study found that CBT delivered by a psychologist reduced the impact of hot flashes and night sweats at 6 weeks.
The MANCAN2 study assessed QoL at 6 months among 162 patients with localized or advanced prostate cancer who underwent at least 6 months of continuous ADT and who experienced more severe hot flashes and night sweats, defined as a score of ≥ 2 on the hot flashes and night sweats problem rating scale.
Study participants were randomized to CBT plus treatment as usual, or treatment as usual alone, with the intervention consisting of two CBT group sessions 4 weeks apart. Between CBT sessions, patients could refer to a booklet and CD, alongside exercises and CBT strategies.
MANCAN2 confirmed that CBT was associated with a significantly greater reduction in hot flash and night sweat scores over standard care alone at 6 weeks. Patients receiving CBT also reported better QoL, sleep, and functional status but those differences did not reach statistical significance.
By 6 months, those in the CBT group still reported better outcomes in each category, but no differences were statistically significant at this time point. Overall, however, 14% of treatment as usual alone patients discontinued ADT at 6 months vs none in the CBT arm.
“Further research is therefore needed to determine whether or not you can make this effect more durable” and to look at “the potential for CBT to support treatment compliance,” said study presenter Simon J. Crabb, PhD, MBBS, from the University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, England.
QoL With Radioligand Crossover
Finally, the phase 3 PSMAfore study compared 177Lu-PSMA-617 with abiraterone or enzalutamide in 468 taxane-naive patients with metastatic castration-resistant prostate cancer who had progressed on a previous androgen receptor pathway inhibitor.
In earlier analyses, Karim Fizazi, MD, PhD, Institut Gustave Roussy, Université Paris-Saclay, Paris, France, reported that 177Lu-PSMA-617 improved radiographic progression-free survival by 59% over androgen receptor pathway inhibitor therapy but did not lead to significant differences in overall survival.
In a new interim analysis, Dr. Fizazi and colleagues explored outcomes in patients eligible to cross over to 177Lu-PSMA-617 following androgen receptor pathway inhibitor therapy. Assessments of health-related QoL revealed that 177Lu-PSMA-617 led to about a 40% improvement in scores on two QoL tools — 41% with FACT-P and 39% with EuroQol-5D.
On subscales of FACT-P, Dr. Fizazi reported that 177Lu-PSMA-617 was also associated with a significantly longer time to worsening in physical, functional, and emotional well-being over standard therapy. A pain inventory score indicated that 177Lu-PSMA-617 led to a 31% improvement in the time to worsening pain intensity, as well as a 33% increase in the time to worsening pain interference.
With the treatment having a “favorable safety profile,” Dr. Fizazi said the results suggest 177Lu-PSMA-617 is a “treatment option” for patients with metastatic castration-resistant prostate cancer who have undergone androgen receptor pathway inhibitor treatment.
MANCAN2 was funded by the UK National Institute for Health and Care Research. EMBARK was funded by Astellas Pharma and Pfizer, the codevelopers of enzalutamide. PRESTO was funded by Alliance Foundation Trials and Johnson & Johnson. PSMAfore was funded by Novartis. Dr. Freedland declared relationships with Pfizer and Astellas Pharma, among others. Paller declared relationships with AstraZeneca, Dendreon, Exelixis, Janssen Oncology, Omnitura, Lilly, and Bayer. Dr. Chen declared relationships with Astellas Pharma, Pfizer, and others. Dr. Crabb declared relationships with AstraZeneca, Bristol-Myers Squibb, Ipsen, Merck, Amgen, Amphista Therapeutics, Bayer, Janssen, MSD, Pfizer, Astex Pharmaceuticals, Clovis Oncology, and Roche. Dr. Fizazi reported relationships with Novartis, AstraZeneca, and a dozen other companies.
A version of this article first appeared on Medscape.com.
A central aim of prostate cancer treatment is to prolong survival, but trials often overlook another key goal: Improving — or at least maintaining — quality of life (QoL).
The trials explored the effects of treatment suspension or intensification on health-related QoL as well as interventions to manage side effects in different patient populations.
The first presentation focused on a post hoc analysis of the phase 3 EMBARK trial, which looked at the effect of suspending treatment on health-related QoL in men with nonmetastatic disease at a high risk for biochemical recurrence.
Earlier findings from the trial, presented at ESMO in 2023, showed enzalutamide alone or in combination with androgen deprivation therapy (ADT) was associated with a significant improvement in metastasis-free survival vs placebo plus leuprolide.
The initial trial randomized 1068 patients at a high risk for biochemical recurrence to these three treatment groups and suspended therapy at week 37 if prostate-specific antigen (PSA) levels fell below 0.2 ng/mL. Patients, however, were not randomized into the treatment suspension groups. Treatment resumed if PSA levels rose to ≥ 2.0 ng/mL in patients who had undergone radical prostatectomy or ≥ 5.0 ng/mL in those who had not had surgery.
The post hoc analysis, which assessed patient-reported QoL outcomes following treatment suspension at baseline and every 12 weeks until progression, found no meaningful changes in the worst pain in the past 24 hours, as measured by the Brief Pain Inventory–Short Form.
Patients also reported no meaningful changes in total and physical well-being scores on the Functional Assessment of Cancer Therapy–Prostate (FACT-P) and on the European Quality of Life Five-Dimensions (EuroQol-5D) visual analog scale score, as well as no meaningful changes in sexual activity and urinary and bowel symptoms, based on scores from the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire–Prostate 25 (QLQ-PR25).
Hormone treatment-related symptoms on the QLQ-PR25, however, “quickly improved but eventually began to worsen after week 97,” explained lead author Stephen J. Freedland, MD, from Cedars-Sinai Medical Center, Los Angeles, California, who presented the new findings at ASCO.
Dr. Freedland concluded that the EMBARK results show that enzalutamide, with or without ADT, improves metastasis-free survival vs leuprolide alone, without affecting global health-related QoL during treatment or after treatment suspension.
However, Channing J. Paller, MD, of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Medicine, Baltimore, Maryland, who was not involved in the research, pointed out that “patient selection is key” when choosing therapies, given that ADT has distinct adverse effects. Comorbidities and adverse effects “must be taken into consideration to help the doctor and patient make more personalized treatment choices.”
Treatment Intensification and QoL
Another presentation explored health-related QoL outcomes from the phase 3 PRESTO trial.
The study examined ADT intensification in 504 patients who had high-risk biochemically relapsed nonmetastatic hormone-sensitive prostate cancer and a PSA doubling time of 9 months or less. Patients were randomized to ADT monotherapy with degarelix or leuprolide, ADT plus apalutamide, or ADT plus apalutamide, abiraterone acetate, and prednisone.
In previous data from PRESTO, the combination therapy groups both had significantly longer median PSA progression-free survival than the ADT monotherapy arm.
The latest data looked at the health-related QoL outcomes in the PRESTO population, measured using the Expanded Prostate Cancer Index Composite, the PROMIS Fatigue tool, the Hot Flash Related Daily Interference Scale, and the EuroQol-5D.
Ronald C. Chen, MD, MPH, of the University of Kansas Medical Center, Kansas City, who presented the new findings at ASCO, reported that ADT plus apalutamide improved PSA progression-free survival over ADT alone and did not meaningfully increase common treatment-related symptoms, such as hormonal symptoms, sexual dysfunction, hot flash interference, and fatigue.
However, treatment intensification with triple androgen regimen did not lead to further improvements in PSA progression-free survival but did increase the rate of serious adverse events, the time to testosterone recover, and increased hot flash interference.
PRESTO as well as EMBARK “provide a strong rationale for intensification of androgen blockade in men with high-risk biochemical recurrence after completing primary local therapy” and could even “reduce the need for subsequent treatment,” concluded Dr. Chen.
CBT for Managing ADT Side Effects
Up to 80% of men receiving ADT to treat prostate cancer experience night sweats and hot flashes, which are associated with sleep disturbance, anxiety, low mood, and cognitive impairments.
A third trial presented during the session looked at the impact of cognitive-behavioral therapy (CBT) on these side effects of ADT treatment.
Initial findings from the MANCAN study found that CBT delivered by a psychologist reduced the impact of hot flashes and night sweats at 6 weeks.
The MANCAN2 study assessed QoL at 6 months among 162 patients with localized or advanced prostate cancer who underwent at least 6 months of continuous ADT and who experienced more severe hot flashes and night sweats, defined as a score of ≥ 2 on the hot flashes and night sweats problem rating scale.
Study participants were randomized to CBT plus treatment as usual, or treatment as usual alone, with the intervention consisting of two CBT group sessions 4 weeks apart. Between CBT sessions, patients could refer to a booklet and CD, alongside exercises and CBT strategies.
MANCAN2 confirmed that CBT was associated with a significantly greater reduction in hot flash and night sweat scores over standard care alone at 6 weeks. Patients receiving CBT also reported better QoL, sleep, and functional status but those differences did not reach statistical significance.
By 6 months, those in the CBT group still reported better outcomes in each category, but no differences were statistically significant at this time point. Overall, however, 14% of treatment as usual alone patients discontinued ADT at 6 months vs none in the CBT arm.
“Further research is therefore needed to determine whether or not you can make this effect more durable” and to look at “the potential for CBT to support treatment compliance,” said study presenter Simon J. Crabb, PhD, MBBS, from the University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, England.
QoL With Radioligand Crossover
Finally, the phase 3 PSMAfore study compared 177Lu-PSMA-617 with abiraterone or enzalutamide in 468 taxane-naive patients with metastatic castration-resistant prostate cancer who had progressed on a previous androgen receptor pathway inhibitor.
In earlier analyses, Karim Fizazi, MD, PhD, Institut Gustave Roussy, Université Paris-Saclay, Paris, France, reported that 177Lu-PSMA-617 improved radiographic progression-free survival by 59% over androgen receptor pathway inhibitor therapy but did not lead to significant differences in overall survival.
In a new interim analysis, Dr. Fizazi and colleagues explored outcomes in patients eligible to cross over to 177Lu-PSMA-617 following androgen receptor pathway inhibitor therapy. Assessments of health-related QoL revealed that 177Lu-PSMA-617 led to about a 40% improvement in scores on two QoL tools — 41% with FACT-P and 39% with EuroQol-5D.
On subscales of FACT-P, Dr. Fizazi reported that 177Lu-PSMA-617 was also associated with a significantly longer time to worsening in physical, functional, and emotional well-being over standard therapy. A pain inventory score indicated that 177Lu-PSMA-617 led to a 31% improvement in the time to worsening pain intensity, as well as a 33% increase in the time to worsening pain interference.
With the treatment having a “favorable safety profile,” Dr. Fizazi said the results suggest 177Lu-PSMA-617 is a “treatment option” for patients with metastatic castration-resistant prostate cancer who have undergone androgen receptor pathway inhibitor treatment.
MANCAN2 was funded by the UK National Institute for Health and Care Research. EMBARK was funded by Astellas Pharma and Pfizer, the codevelopers of enzalutamide. PRESTO was funded by Alliance Foundation Trials and Johnson & Johnson. PSMAfore was funded by Novartis. Dr. Freedland declared relationships with Pfizer and Astellas Pharma, among others. Paller declared relationships with AstraZeneca, Dendreon, Exelixis, Janssen Oncology, Omnitura, Lilly, and Bayer. Dr. Chen declared relationships with Astellas Pharma, Pfizer, and others. Dr. Crabb declared relationships with AstraZeneca, Bristol-Myers Squibb, Ipsen, Merck, Amgen, Amphista Therapeutics, Bayer, Janssen, MSD, Pfizer, Astex Pharmaceuticals, Clovis Oncology, and Roche. Dr. Fizazi reported relationships with Novartis, AstraZeneca, and a dozen other companies.
A version of this article first appeared on Medscape.com.
FROM ASCO 2024