'Treatment Holiday' in Prostate Cancer With Tailored Dosing

Roxanne Nelson, RN, BSN

July 25, 2023

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, Australia.

The research was presented at the Society of Nuclear Medicine and Molecular Imaging 2023 annual meeting.

Although clinical trials have demonstrated that 177Lu-PSMA is an effective treatment for metastatic castratioin-resistant prostate cancer, the question remains: Can patient outcomes by improved through the use of biomarkers and by escalating or deescalating treatment as appropriate? asked 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, 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, 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 castrate-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.

Nguyen noted several limitations to the findings, including the study's retrospective nature and 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 cross-over to potentially more effective therapies in nonresponders," the authors conclude.

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

Society of Nuclear Medicine and Molecular Imaging: Abstract 507. Presented on June 27, 2023.

Roxanne Nelson is a registered nurse and an award-winning medical writer who has written for many major news outlets and is a regular contributor to Medscape.

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