Personalized Dosing May Improve Outcomes in Patients With Prostate Cancer
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.
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.
“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.The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.