By monitoring early-response biomarkers in men undergoing 177Lu-PSMA prostate cancer treatment, physicians can personalise dosing intervals, significantly improving patient outcomes.

In a study presented at the Society of Nuclear Medicine and Molecular Imaging 2023 Annual Meeting, early stratification with 177Lu-SPECT/CT allowed men responding to treatment to take a “treatment holiday” and allowed those not responding the option to switch to another treatment. 

Approved by the US Food and Drug Administration in 2022, 177Lu-PSMA is an effective treatment for metastatic castration-resistant prostate cancer.

However, not all men respond equally to treatment, with some responding very well and others progressing early.  

“Currently, a standardised dosing interval is used for 177Lu-PSMA treatment,” said Andrew Nguyen, MBBS, FRACP, AANMS, senior staff specialist in the Department of Theranostics and Nuclear Medicine at St Vincent's Hospital in Sydney, Australia.

“However, monitoring early-response biomarkers to adjust treatment intervals may improve patient outcomes.”  

In the study, researchers sought to evaluate progression-free survival and overall survival of different dosing intervals. Study participants included 125 men who were treated in a clinical program with six weekly doses of 177Lu-PSMA. The men were imaged with 177Lu-SPECT/CT after each dose.

After the second dose, researchers analysed the men’s prostate specific antigen (PSA) levels and the 177Lu-SPECT response to determine ongoing management.  

Patients were grouped by level of response.

Those in Response Group 1 (35 percent of participants) had a marked reduction in PSA level and partial response on 177Lu-SPECT and were advised to cease treatment until PSA levels rose.

Response Group 2 (34 percent) saw stable or reduced PSA and stable disease on SPECT imaging; these men continued on their six week treatment plan until no longer clinically beneficial.

In Response Group 3 (31 percent), men saw a rise in PSA levels and had progressive disease on SPECT imaging. These patients were offered the opportunity to try a different treatment.  

PSA levels decreased by more than 50 percent in 60 percent of patients.

Overall study participants had a median PSA progression-free survival of 6.1 months and a median overall survival of 16.8 months.

Median PSA progression-free survival was 12.1 months, 6.1 months, and 2.6 months, for Response Groups 1, 2 and 3, respectively.

The overall survival was 19.2 months for Response Group 1, 13.2 months for Response Group 2, and 11. 2 months for Response Group 3.

Additionally, for those in Response Group 1 who had a “treatment holiday,” the median treatment-free time was 6.1 months.  

“Personalised dosing allowed one-third of the men in this study to have treatment breaks while still achieving the same progression-free and overall survival outcomes they would have if they received continuous treatment,” noted Nguyen.

“It also allowed another one-third of men who had early biomarkers of disease progression the opportunity to try a more effective potential therapy if one was available.” 

Patients at St Vincent's Hospital will continue to be stratified by these early response biomarkers.

Once validated in a prospective clinical trial, Nguyen hopes that this stratification strategy will become more widely available for patients. 

Source: Society of Nuclear Medicine and Molecular Imaging