Prognostic role of early prostate specific antigen changes after [<scp><sup>177</sup>Lu</scp>]<scp>Lu‐PSMA</scp> radioligand therapy of metastasized prostate cancer: A <scp>meta‐analysis</scp>

Giovanella, Luca; Garo, Maria Luisa; Cuzzocrea, Marco; Paone, Gaetano; Herrmann, Ken

doi:10.1111/eci.14014

Cited by 5 publications

(1 citation statement)

References 52 publications

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“…Whether it is more useful earlier in the course of disease is still unclear; although response rates and survival appear better with taxane-naive patients, 48 and early results from the PSMAfore trial suggest radiographic progression-free survival may be better with 177 Lu-PSMA than switching androgen-receptor pathway inhibitors after 1 ARPI has failed, 49 further study remains necessary. A meta-analysis of 12 studies suggests PSA decline at 12 weeks may indicate whether the therapy will be effective 50 …”

Section: Radioligand Therapymentioning

confidence: 99%

PSMA-Targeted Radiopharmaceuticals for Prostate Cancer Diagnosis and Therapy

Oldan,

Almaguel,

Voter

et al. 2024

Cancer J

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Prostate cancer (PCa) is the most common noncutaneous malignancy in men. Until recent years, accurate imaging of men with newly diagnosed PCa, or recurrent or low-volume metastatic disease, was limited. Further, therapeutic options for men with advanced, metastatic, castration-resistant disease were increasingly limited as a result of increasing numbers of systemic therapies being combined in the upfront metastatic setting. The advent of urea-based, small-molecule inhibitors of prostate-specific membrane antigen (PSMA) has partially addressed those shortcomings in diagnosis and therapy of PCa. On the diagnostic side, there are multiple pivotal phase III trials with several different agents having demonstrated utility in the initial staging setting, with generally modest sensitivity but very high specificity for determining otherwise-occult pelvic nodal involvement. That latter statistic drives the utility of the scan by allowing imaging interpreters to read with very high sensitivity while maintaining a robust specificity. Other pivotal phase III trials have demonstrated high detection efficiency in patients with biochemical failure, with high positive predictive value at the lesion level, opening up possible new avenues of therapy such as metastasis-directed therapy. Beyond the diagnostic aspects of PSMA-targeted radiotracers, the same urea-based chemical scaffolds can be altered to deliver therapeutic isotopes to PCa cells that express PSMA. To date, one such agent, when combined with best standard-of-care therapy, has demonstrated an ability to improve overall survival, progression-free survival, and freedom from skeletal events relative to best standard-of-care therapy alone in men with metastatic, castration-resistant PCa who are post chemotherapy. Within the current milieu, there are a number of important future directions including the use of artificial intelligence to better leverage diagnostic findings, further medicinal chemistry refinements to the urea-based structure that may allow improved tumor targeting and decreased toxicities, and the incorporation of new radionuclides that may better balance efficacy with toxicities than those nuclides that are available.

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Section: Radioligand Therapymentioning

confidence: 99%

PSMA-Targeted Radiopharmaceuticals for Prostate Cancer Diagnosis and Therapy

Oldan,

Almaguel,

Voter

et al. 2024

Cancer J

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Efficacy and safety of rechallenge with [177Lu]Lu-PSMA-I&T radioligand therapy in metastatic castration resistant prostate cancer

Santo,

Di Santo,

Sviridenko

et al. 2024

Eur J Nucl Med Mol Imaging

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Background The purpose of this study was to evaluate the safety and outcome of rechallenge [177Lu]Lu-PSMA-I&T in newly progressed mCRPC patients after response to initial [177Lu]Lu-PSMA radioligand therapy (PRLT). Methods We retrospectively included 18 patients who underwent rechallenge with [177Lu]Lu-PSMA-I&T. All patients presented with (i) newly progressed disease after response to initial PRLT; (ii) a [68Ga]Ga-PSMA-11 PET/CT confirming the presence of PSMA-positive metastases; iii) ECOG performance status 0–1. Adverse events were graded according to CTCAE v5.0. Response was assessed by PSA and classified according to PCWG3 recommendations. For patients who underwent restaging with [68Ga]Ga-PSMA-11 PET/CT, imaging response was categorised according to adapted PERCIST v1.0. In patients with discordant [68Ga]Ga-PSMA-11 PET/CT and PSA, other available imaging modalities were evaluated to confirm disease status. Overall survival (OS) was calculated from the first cycle of initial PRLT and rechallenge PRLT, respectively, until last patient contact or death. Results Patients were initially treated with a median of 5 cycles (range 4–7) and were rechallenged after a median of 9 months (range 3–13). Each patient received a median of 4 (range 2–7) rechallenge cycles (median cumulative activity 26.1 GBq). None of the patients experienced life-threatening G4 adverse events during either treatment period. Grade 3 adverse events included one case of anaemia, one case of thrombocytopenia, and one case of renal failure. In 8/18 patients long-term toxicities were evaluated. Serious toxicities (≥ Grade 3) occurred in 3/8 patients (n = 1 G4 thrombocytopenia, n = 1 G4 renal failure and n = 1 pancytopenia and G4 renal failure). Best PSA50%-response was observed in 44% of patients and PSA-disease control was confirmed in 56% of patients at the last cycle. Of the 12/18 patients restaged by imaging, 6/12 (50%) patients had disease control (partial response/stable disease), 1/12 had a mixed response, and 5/12 had progression. After a median follow-up time of 25 months (range 14–44), 10 patients had died, 7 were still alive, and one patient was lost at follow-up. The median OS was 29 months (95%CI, 14.3–43.7 months) for the initial treatment and 11 months (95%CI, 8.1–13.8 months) for the first rechallenge course. Conclusion More than half of patients benefit from rechallenge PRLT. Our analysis suggests that rechallenge may prolong survival in selected patients, with an acceptable safety profile.

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177Lu-PSMA therapy in metastatic prostate cancer: An updated review of prognostic and predictive biomarkers

Giunta,

Brighi,

Gurioli

et al. 2024

Cancer Treatment Reviews

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Prognostic role of early prostate specific antigen changes after [¹⁷⁷Lu]Lu‐PSMA radioligand therapy of metastasized prostate cancer: A meta‐analysis

Cited by 5 publications

References 52 publications

PSMA-Targeted Radiopharmaceuticals for Prostate Cancer Diagnosis and Therapy

PSMA-Targeted Radiopharmaceuticals for Prostate Cancer Diagnosis and Therapy

Efficacy and safety of rechallenge with [177Lu]Lu-PSMA-I&T radioligand therapy in metastatic castration resistant prostate cancer

177Lu-PSMA therapy in metastatic prostate cancer: An updated review of prognostic and predictive biomarkers

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Prognostic role of early prostate specific antigen changes after [177Lu]Lu‐PSMA radioligand therapy of metastasized prostate cancer: A meta‐analysis

Cited by 5 publications

References 52 publications

PSMA-Targeted Radiopharmaceuticals for Prostate Cancer Diagnosis and Therapy

PSMA-Targeted Radiopharmaceuticals for Prostate Cancer Diagnosis and Therapy

Efficacy and safety of rechallenge with [177Lu]Lu-PSMA-I&T radioligand therapy in metastatic castration resistant prostate cancer

177Lu-PSMA therapy in metastatic prostate cancer: An updated review of prognostic and predictive biomarkers

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Prognostic role of early prostate specific antigen changes after [¹⁷⁷Lu]Lu‐PSMA radioligand therapy of metastasized prostate cancer: A meta‐analysis