Timing between 177Lu-PSMA doses shows no impact on survival in patients with mCRPC

Patients with metastatic castrate-resistant prostate cancer (mCRPC) who underwent treatment with ¹⁷⁷Lu-PSMA at adjusted intervals based on early response biomarkers showed similar overall survival (OS) and progression-free survival (PFS) to patients who underwent the treatment with continuous dosing.¹

Investigators analyzed data from 125 men with mCRPC were treated with 6-weekly ¹⁷⁷Lu-PSMA-I&T at a median dose of 8.0 GBq.

The data were presented at the 2023 Society of Nuclear Medicine and Molecular Imaging Annual Meeting in Chicago, Illinois.¹

“Personalized 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. 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,” said Andrew Nguyen, MBBS, FRACP, AANMS, in a news release on the findings.² Nguyen is a senior staff specialist in the department of theranostics and nuclear medicine at St. Vincent's Hospital in Sydney, Australia.

For the study, investigators analyzed data from 125 men with mCRPC were treated with 6-weekly ¹⁷⁷Lu-PSMA-I&T at a median dose of 8.0 GBq. All participants were imaged with ¹⁷⁷LuPSMA 24-h SPECT/CT following each dose. Prostate-specific antigen (PSA) levels and changes in tumor volume on a SPECT scan were used as biomarkers for response.

Patients were retrospectively divided into 3 groups based on response to treatment. In total, 9 men were not assigned to a response group, and they received prior treatment with ¹⁷⁷LuPSMA-617 and were retreated with ¹⁷⁷LuPSMA-I&T. Patients in group 1 (41/116, 35%) received a break in treatment following reduction in PSA level and began treatment again following a rise in PSA. Median treatment-free time for patients in this group was 6.1 months. Patients in group 2 (39/116, 34%) received standard dosing of ¹⁷⁷Lu-PSMA until 6 doses or no longer clinically benefitting. Patients in group 3 (36/116, 31%) demonstrated a rise in PSA and were recommended an alternative treatment.

Overall, 60% of patients included in the study experienced a PSA decrease of more than 50%. Median PSA PFS among all participants was 6.1 months, and median OS among all participants was 16.8 months.

When divided by response groups, median PSA PFS was 12.1 months (95% CI: 9.3-17.4) among patients in group 1, compared with 6.1 months (95% CI: 5.8-9.0) among patients in group 2 and 2.6 months (95% CI: 1.6-3.1) among patients in group 3. Further, median OS among patients in group 1 was 19.2 months (95% CI: 16.8-20.7), compared with 13.2 months (95% CI: 12.0-18.8) among patients in group 2 and 11.2 months among patients in group 3 (95% CI: 8.7-15.6).

Nguyen concluded, “Personalizing dosing regimens using composite early response biomarkers with ¹⁷⁷LuPSMA SPECT, diagnostic CT, and PSA has the potential to achieve similar treatment responses to continuous dosing while allowing treatment breaks or intensification. Further evaluation in prospective trials is warranted.”

References

1. Emmett L, John N, Pathmanandavel S, et al. Patient outcomes following a response biomarker-guided approach to treatment using ¹⁷⁷Lu-PSMA-I&T in men with metastatic castrate-resistant prostate cancer (Re-SPECT). The Adv Med Oncol. Published online March 1, 2023. Accessed June 29, 2023. doi:10.1177/17588359231156392

2. Personalized dosing in prostate cancer treatment improves patient outcomes. News release. Society of Nuclear Medicine and Molecular Imaging. June 27, 2023. Accessed June 29, 2023. https://www.snmmi.org/NewsPublications/NewsDetail.aspx?ItemNumber=44241