Physicians may be able to personalize dosing intervals and consequently improve patient outcomes by monitoring early-response biomarkers in patients with prostate cancer who are undergoing treatment with lutetium (Lu)-177–PSMA, according to new findings presented by Emmett et al at the Society of Nuclear Medicine & Molecular Imaging 2023 Annual Meeting (Abstract 507). The research suggested that early stratification with Lu-177–single-photon emission computed tomography (SPECT)/computed tomography (CT) allowed patients who responded to therapy to take a break from the treatment and those who did not respond to switch to another therapy.
Background
Since it was approved by the U.S. Food and Drug Administration in 2022, Lu-177–PSMA has proven effective at treating patients with metastatic castration-resistant prostate cancer. However, not all patients respond equally to the agent—with some responding well and others experiencing disease progression early.
“Currently, a standardized dosing interval is used for [Lu-177–PSMA] treatment,” explained senior study author Andrew Nguyen, MBBS, FRACP, AANMS, a 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,” he emphasized.
Study Methods and Results
In the new study, researchers evaluated the progression-free survival and overall survival of different dosing intervals in 125 patients with prostate cancer who underwent a regimen of six weekly doses of Lu-177–PSMA. The patients were imaged with Lu-177–SPECT/CT after each dose. After the second dose, the researchers analyzed the patients’ prostate-specific antigen (PSA) levels and the Lu-177–SPECT responses to determine ongoing management.
They then grouped the patients by level of response. Those in response group 1, which included 35% of the patients, demonstrated marked reductions in PSA levels and partial responses on Lu-177–SPECT and were advised to cease treatment until their PSA levels rose. Those in response group 2 (34%) saw stable or reduced PSA levels as well as stable disease on SPECT imaging; these patients continued on their 6-week treatment plan until it was no longer clinically beneficial. Those in response group 3 (31%) experienced increases in their PSA levels and had progressive disease on SPECT imaging. These patients were offered the opportunity to switch to a different therapy.
Further, the researchers discovered that PSA levels decreased by more than 50% in 60% of the patients. The patients involved in the study had a median progression-free survival of 6.1 months and a median overall survival of 16.8 months. Median progression-free survival was 12.1 months, 6.1 months, and 2.6 months; and overall survival was 19.2 months, 13.2 months, and 11. 2 months for response groups 1, 2, and 3, respectively. Additionally, for those in response group 1 who were able to take a break from treatment, the median treatment-free time was 6.1 months.
Conclusions
“Personalized dosing allowed one-third of the [patients] 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,” underscored Dr. Nguyen. “It also allowed another one-third of [the patients] who had early biomarkers of disease progression the opportunity to try a more effective potential therapy if one was available,” he concluded.
The researchers plan to continue stratifying the patients by these early response biomarkers. Once validated in a prospective clinical trial, they hope that this stratification strategy will become more widely available for patients.
