‘Treatment holiday’ in prostate cancer with tailored dosing

Monitoring early-response biomarkers in patients receiving lutetium-177 (¹⁷⁷Lu)–PSMA-617 for metastatic castrate-resistant prostate cancer may allow physicians to personalize dosing intervals and improve patient outcomes, new research suggests.

The findings indicate that implementing a personalized dosing strategy with the radioligand therapy “allowed for treatment holidays in excellent responders, continuous 6-weekly treatments in moderate responders, and [allowed us] to consider changing or adding treatment in limited responders,” said study author Andrew Nguyen, MBBS, FRACP, AANMS, senior staff specialist in the department of theranostics and nuclear medicine at St. Vincent’s Hospital in Sydney.

The research was presented at the annual meeting of the Society of Nuclear Medicine and Molecular Imaging.

Although clinical trials have demonstrated that ¹⁷⁷Lu-PSMA is an effective treatment for metastatic castration-resistant prostate cancer, the question remains: Can patient outcomes be improved through the use of biomarkers and by escalating or deescalating treatment as appropriate? asked Dr. Nguyen, who presented the findings at the meeting.

Clinical trials use standardized dosing intervals. Adjusting treatment intervals through the use of early-biomarker responses could give some patients a break from treatment and improve overall survival outcomes, Dr. Nguyen explained. For example, the 2021 REALITY study showed that overall survival was significantly better for patients who received ¹⁷⁷Lu-PSMA plus standard care, compared with patients who received standard care alone (median, 15.3 vs. 11.3 months), and that overall survival was better among patients with early prostate-specific antigen (PSA) responses.

In the current study, Dr. Nguyen and colleagues used composite early biomarkers of PSA, imaging with 1⁷⁷Lu-PSMA SPECT, and diagnostic CT to guide a personalized dosing interval strategy for patients with metastatic castration-resistant prostate cancer receiving ¹⁷⁷Lu-PSMA. The team evaluated progression-free survival and overall survival among these patients to determine whether personalizing dosing on the basis of early biomarker levels was associated with survival outcomes.

The cohort included 125 men who received six weekly doses of ¹⁷⁷Lu-PSMA and who underwent imaging with ¹⁷⁷Lu-SPECT/CT after each dose. After the second dose, investigators used the composite of PSA and ¹⁷⁷Lu SPECT/CT response to determine which patients had a partial response, which had stable disease, and which had progressive disease.

The men were divided into three groups on the basis of their level of response. Group 1, which included 35% of participants, achieved a significant reduction in PSA levels and a partial response on ¹⁷⁷Lu-SPECT. These patients were advised to discontinue treatment until PSA levels increased. This treatment holiday lasted a median of about 6 months.

Group 2, which represented 34% of the cohort, had stable or reduced PSA levels as well as stable disease on SPECT imaging. For these patients, the treatment regimen continued.

Group 3 demonstrated rising PSA levels and progressive disease on SPECT imaging. These men were offered an alternative therapy.

Overall, median PSA progression-free survival was 12.1 months in group 1, 6.1 months in group 2, and 2.6 months in group 3. Median overall survival was also significantly better among patients who showed early responses to therapy: 19.2 months in group 1, 13.2 months in group 2, and 11. 2 months in group 3.

Dr. Nguyen noted several limitations to the findings, including the study’s retrospective nature and the fact that some patients in group 1 chose not to resume further treatment after their PSA levels rose.

“Personalizing dosing intervals using early-response biomarkers with ¹⁷⁷Lu-PSMA has the potential to achieve similar overall treatment responses to that published for continuous dosing, while allowing treatment holidays in responders and early crossover to potentially more effective therapies in nonresponders,” the authors conclude.

Given the effectiveness of this strategy, Dr. Nguyen says his team “now routinely uses these composite biomarkers when treating clinical patients.”

A version of this article appeared on Medscape.com.

Monitoring early-response biomarkers in patients receiving lutetium-177 (¹⁷⁷Lu)–PSMA-617 for metastatic castrate-resistant prostate cancer may allow physicians to personalize dosing intervals and improve patient outcomes, new research suggests.

The findings indicate that implementing a personalized dosing strategy with the radioligand therapy “allowed for treatment holidays in excellent responders, continuous 6-weekly treatments in moderate responders, and [allowed us] to consider changing or adding treatment in limited responders,” said study author Andrew Nguyen, MBBS, FRACP, AANMS, senior staff specialist in the department of theranostics and nuclear medicine at St. Vincent’s Hospital in Sydney.

The research was presented at the annual meeting of the Society of Nuclear Medicine and Molecular Imaging.

Although clinical trials have demonstrated that ¹⁷⁷Lu-PSMA is an effective treatment for metastatic castration-resistant prostate cancer, the question remains: Can patient outcomes be improved through the use of biomarkers and by escalating or deescalating treatment as appropriate? asked Dr. Nguyen, who presented the findings at the meeting.

Clinical trials use standardized dosing intervals. Adjusting treatment intervals through the use of early-biomarker responses could give some patients a break from treatment and improve overall survival outcomes, Dr. Nguyen explained. For example, the 2021 REALITY study showed that overall survival was significantly better for patients who received ¹⁷⁷Lu-PSMA plus standard care, compared with patients who received standard care alone (median, 15.3 vs. 11.3 months), and that overall survival was better among patients with early prostate-specific antigen (PSA) responses.

In the current study, Dr. Nguyen and colleagues used composite early biomarkers of PSA, imaging with 1⁷⁷Lu-PSMA SPECT, and diagnostic CT to guide a personalized dosing interval strategy for patients with metastatic castration-resistant prostate cancer receiving ¹⁷⁷Lu-PSMA. The team evaluated progression-free survival and overall survival among these patients to determine whether personalizing dosing on the basis of early biomarker levels was associated with survival outcomes.

The cohort included 125 men who received six weekly doses of ¹⁷⁷Lu-PSMA and who underwent imaging with ¹⁷⁷Lu-SPECT/CT after each dose. After the second dose, investigators used the composite of PSA and ¹⁷⁷Lu SPECT/CT response to determine which patients had a partial response, which had stable disease, and which had progressive disease.

The men were divided into three groups on the basis of their level of response. Group 1, which included 35% of participants, achieved a significant reduction in PSA levels and a partial response on ¹⁷⁷Lu-SPECT. These patients were advised to discontinue treatment until PSA levels increased. This treatment holiday lasted a median of about 6 months.

Group 2, which represented 34% of the cohort, had stable or reduced PSA levels as well as stable disease on SPECT imaging. For these patients, the treatment regimen continued.

Group 3 demonstrated rising PSA levels and progressive disease on SPECT imaging. These men were offered an alternative therapy.

Overall, median PSA progression-free survival was 12.1 months in group 1, 6.1 months in group 2, and 2.6 months in group 3. Median overall survival was also significantly better among patients who showed early responses to therapy: 19.2 months in group 1, 13.2 months in group 2, and 11. 2 months in group 3.

Dr. Nguyen noted several limitations to the findings, including the study’s retrospective nature and the fact that some patients in group 1 chose not to resume further treatment after their PSA levels rose.

“Personalizing dosing intervals using early-response biomarkers with ¹⁷⁷Lu-PSMA has the potential to achieve similar overall treatment responses to that published for continuous dosing, while allowing treatment holidays in responders and early crossover to potentially more effective therapies in nonresponders,” the authors conclude.

Given the effectiveness of this strategy, Dr. Nguyen says his team “now routinely uses these composite biomarkers when treating clinical patients.”

A version of this article appeared on Medscape.com.

Monitoring early-response biomarkers in patients receiving lutetium-177 (¹⁷⁷Lu)–PSMA-617 for metastatic castrate-resistant prostate cancer may allow physicians to personalize dosing intervals and improve patient outcomes, new research suggests.

The findings indicate that implementing a personalized dosing strategy with the radioligand therapy “allowed for treatment holidays in excellent responders, continuous 6-weekly treatments in moderate responders, and [allowed us] to consider changing or adding treatment in limited responders,” said study author Andrew Nguyen, MBBS, FRACP, AANMS, senior staff specialist in the department of theranostics and nuclear medicine at St. Vincent’s Hospital in Sydney.

The research was presented at the annual meeting of the Society of Nuclear Medicine and Molecular Imaging.

Although clinical trials have demonstrated that ¹⁷⁷Lu-PSMA is an effective treatment for metastatic castration-resistant prostate cancer, the question remains: Can patient outcomes be improved through the use of biomarkers and by escalating or deescalating treatment as appropriate? asked Dr. Nguyen, who presented the findings at the meeting.

Clinical trials use standardized dosing intervals. Adjusting treatment intervals through the use of early-biomarker responses could give some patients a break from treatment and improve overall survival outcomes, Dr. Nguyen explained. For example, the 2021 REALITY study showed that overall survival was significantly better for patients who received ¹⁷⁷Lu-PSMA plus standard care, compared with patients who received standard care alone (median, 15.3 vs. 11.3 months), and that overall survival was better among patients with early prostate-specific antigen (PSA) responses.

In the current study, Dr. Nguyen and colleagues used composite early biomarkers of PSA, imaging with 1⁷⁷Lu-PSMA SPECT, and diagnostic CT to guide a personalized dosing interval strategy for patients with metastatic castration-resistant prostate cancer receiving ¹⁷⁷Lu-PSMA. The team evaluated progression-free survival and overall survival among these patients to determine whether personalizing dosing on the basis of early biomarker levels was associated with survival outcomes.

The cohort included 125 men who received six weekly doses of ¹⁷⁷Lu-PSMA and who underwent imaging with ¹⁷⁷Lu-SPECT/CT after each dose. After the second dose, investigators used the composite of PSA and ¹⁷⁷Lu SPECT/CT response to determine which patients had a partial response, which had stable disease, and which had progressive disease.

The men were divided into three groups on the basis of their level of response. Group 1, which included 35% of participants, achieved a significant reduction in PSA levels and a partial response on ¹⁷⁷Lu-SPECT. These patients were advised to discontinue treatment until PSA levels increased. This treatment holiday lasted a median of about 6 months.

Group 2, which represented 34% of the cohort, had stable or reduced PSA levels as well as stable disease on SPECT imaging. For these patients, the treatment regimen continued.

Group 3 demonstrated rising PSA levels and progressive disease on SPECT imaging. These men were offered an alternative therapy.

Overall, median PSA progression-free survival was 12.1 months in group 1, 6.1 months in group 2, and 2.6 months in group 3. Median overall survival was also significantly better among patients who showed early responses to therapy: 19.2 months in group 1, 13.2 months in group 2, and 11. 2 months in group 3.

Dr. Nguyen noted several limitations to the findings, including the study’s retrospective nature and the fact that some patients in group 1 chose not to resume further treatment after their PSA levels rose.

“Personalizing dosing intervals using early-response biomarkers with ¹⁷⁷Lu-PSMA has the potential to achieve similar overall treatment responses to that published for continuous dosing, while allowing treatment holidays in responders and early crossover to potentially more effective therapies in nonresponders,” the authors conclude.

Given the effectiveness of this strategy, Dr. Nguyen says his team “now routinely uses these composite biomarkers when treating clinical patients.”

A version of this article appeared on Medscape.com.