Metastatic Prostate Cancer
Patient Selection and Treatment Personalization With Prostate-Specific Membrane Antigen–Directed Radioligand Therapy
Researchers at the 2023 Society of Nuclear Medicine & Molecular Imaging (SNMMI) Annual Meeting presented data that may inspire the further study of the individualization of prostate-specific membrane antigen (PSMA)–targeted radioligand therapy.
Conference Reporter Editor-in-Chief Tom Iarocci, MD, previewed several presentations from the conference, summarizing important findings here.
Editor-in-Chief, Expert Perspectives in Medicine
“In the case of PSMA-targeted radioligand therapy, researchers are just beginning to work on personalized therapy. At the 2023 SNMMI Annual Meeting, several studies reflected early efforts to refine patient selection and optimize therapeutic activity so that more patients can derive the maximal benefit.”
In the setting of previously treated metastatic castration-resistant prostate cancer (mCRPC), where treatment options may become limited, having options can be meaningful to patients and may provide opportunities to individualize treatment. For example, a patient with mCRPC who has progressed after docetaxel and androgen receptor–targeted therapy may be a candidate for cabazitaxel; however, if this individual must travel a good distance to receive treatments, he might prefer 177Lu-PSMA-617 (also referred to as lutetium Lu 177 vipivotide tetraxetan) based on the lower treatment frequency of approximately once every 6 weeks for 4 to 6 cycles.
Personalized treatment also includes tailoring a specific therapy to a specific patient. In the case of PSMA-targeted radioligand therapy, researchers are just beginning to work on personalized therapy. At the 2023 SNMMI Annual Meeting, several studies reflected early efforts to refine patient selection and optimize therapeutic activity so that more patients can derive the maximal benefit.
A few presentations focused on the safety of PSMA-targeted radioligand therapy in patients who may be at greater risk for treatment-related toxicities. For instance, Abdelrazek et al examined the adverse events occurring during or shortly after treatment with 177Lu-PSMA at the Mayo Clinic, identifying 185 eligible patients for analysis (poster P1018). Overall, they found that mild to moderate short-term side effects that are secondary to treatment with 177Lu-PSMA can be mostly managed in an outpatient setting. They also found an association between higher Eastern Cooperative Oncology Group performance scores and increased post-treatment emergency department visits and hospital admissions.
Also at the SNMMI meeting, Langbein and colleagues considered the safety of 177Lu-PSMA-I&T, another 177Lu-PSMA–targeted radioligand therapy that is currently in phase 3 clinical trials, in the 80-and-over age group (poster P1229). They reported that 177Lu-PSMA-I&T in elderly patients with mCRPC was safe and effective, findings that are comparable to previously published data of non–age-selected cohorts. For example, in a previous study of 100 patients by Heck et al, 177Lu-PSMA-I&T showed good activity in more than one-third of patients with late-stage mCRPC at low toxicity.
Patients with mCRPC may vary in their access to PSMA positron emission tomography (PET) imaging based on where they receive care. Clinical trials such as VISION and TheraP both report the efficacy of 177Lu-PSMA-617 therapy utilizing 68Ga-PSMA-11 PET/computed tomography (CT) imaging for patient selection. 68Ga-PSMA-11 received US Food and Drug Administration approval prior to 18F-DCFPyL PSMA PET/CT, but both are now available, so there is interest in whether 18F-DCFPyL can be used much like 68Ga-PSMA-11 to select patients for 177Lu-PSMA-617 treatment.
At the conference, researchers from the University of California, San Francisco pursued this question using available data from their institution (poster P1249). Kim et al identified 61 patients who received 177Lu-PSMA-617 therapy, 35 of whom received 68Ga-PSMA-11 and 26 of whom received 18F-DCFPyL. They found that the physiologic biodistributions for 68Ga-PSMA-11 and 18F-DCFPyL were similar between groups; the best post–177Lu-PSMA-617 therapy response was also similar between groups (ie, prostate-specific antigen–50 in 43% of patients imaged with 68Ga-PSMA-11 and in 47% of those imaged with 18F-DCFPyL). The authors concluded that their findings suggest that individuals may be safely selected for 177Lu-PSMA-617 treatment using either 18F-DCFPyL or 68Ga-PSMA-11, but prospective comparison must be performed.
Ultimately, verifying PSMA positivity with a PSMA PET scan might just be the first step in personalized PSMA-targeted radioligand therapy. Researchers hope to further develop both predictive biomarkers and biomarkers for use in response assessment. For example, in poster P507, also presented at the SNMMI meeting, Emmett and colleagues explored the possibility of personalizing 177Lu-PSMA dosing intervals using early response biomarkers, noting that such strategies might allow for the achievement of similar overall treatment responses to that of standard dosing schedules while allowing for therapy changes in nonresponders or even treatment holidays in excellent responders.
Researchers are also seeking to develop predictive markers other than the presence of the target in the tumors. An example of work in this area from the meeting is a single-center pilot experience by Kulkarni et al, who studied ATM mutations and a reduction in molecular tumor volume on single-photon emission CT/CT as potential predictors of a favorable response to treatment with 177Lu-PSMA-617 (poster P1429). Researchers also noted that future clinical trials will examine the integration of different patient and disease features with individual post-therapeutic dosimetry for further treatment personalization.
Abdelrazek A, Mahmoud A, Childs D, et al. Early adverse events, emergency room visits and hospitalizations after PSMA based RLT: a retrospective analysis from real world theranostics practice [poster P1018]. Poster presented at: 2023 Society of Nuclear Medicine & Molecular Imaging Annual Meeting; June 24-27, 2023; Chicago, IL.
AlSadi R, Bouhali O, Dewji S, Djekidel M. 177Lu-PSMA therapy for metastatic castration-resistant prostate cancer: a mini-review of state-of-the-art. Oncologist. 2022;27(12):e957-e966. doi:10.1093/oncolo/oyac216
de Bono JS, Oudard S, Ozguroglu M, et al; TROPIC Investigators. Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial. Lancet. 2010;376(9747):1147-1154. doi:10.1016/S0140-6736(10)61389-X
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) [poster P507]. Poster presented at: 2023 Society of Nuclear Medicine & Molecular Imaging Annual Meeting; June 24-27, 2023; Chicago, IL.
Heck MM, Tauber R, Schwaiger S, et al. Treatment outcome, toxicity, and predictive factors for radioligand therapy with 177Lu-PSMA-I&T in metastatic castration-resistant prostate cancer. Eur Urol. 2019;75(6):920-926. doi:10.1016/j.eururo.2018.11.016
Hofman MS, Emmett L, Sandhu S, et al; TheraP Trial Investigators and the Australian and New Zealand Urogenital and Prostate Cancer Trials Group. [177Lu]Lu-PSMA-617 versus cabazitaxel in patients with metastatic castration-resistant prostate cancer (TheraP): a randomised, open-label, phase 2 trial. Lancet. 2021;397(10276):797-804. doi:10.1016/S0140-6736(21)00237-3
Kim S, Tuchayi AM, Morley A, et al. Comparison of 18F-DCFPyL and 68Ga-PSMA-11 for 177Lu-PSMA-617 therapy patient selection [poster P1249]. Poster presented at: 2023 Society of Nuclear Medicine & Molecular Imaging Annual Meeting; June 24-27, 2023; Chicago, IL.
Kratochwil C, Fendler WP, Eiber M, et al. Joint EANM/SNMMI procedure guideline for the use of 177Lu-labeled PSMA-targeted radioligand-therapy (177Lu-PSMA-RLT). Eur J Nucl Med Mol Imaging. 2023;50(9):2830-2845. doi:10.1007/s00259-023-06255-8
Kulkarni HR, Maupin K, Forsberg J, et al. Personalized PSMA-directed molecular radiotherapy with identification of favorable genomic and post-therapeutic radiomic parameters: a real-world experience post-FDA-approval of Pluvicto from a single comprehensive U.S. theranostic center [poster P1429]. Poster presented at: 2023 Society of Nuclear Medicine & Molecular Imaging Annual Meeting; June 24-27, 2023; Chicago, IL.
Langbein T, Rauscher I, Knorr K, et al. Safety and efficacy of 177Lu-PSMA-I&T radioligand therapy in octogenarians with metastatic castration-resistant prostate cancer: report on eighty patients over age of eighty [poster P1229]. Poster presented at: 2023 Society of Nuclear Medicine & Molecular Imaging Annual Meeting; June 24-27, 2023; Chicago, IL.
Sartor O, de Bono J, Chi KN, et al; VISION Investigators. Lutetium-177-PSMA-617 for metastatic castration-resistant prostate cancer. N Engl J Med. 2021;385(12):1091-1103. doi:10.1056/NEJMoa2107322
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