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. 2024 Oct 14;14(1):94.
doi: 10.1186/s13550-024-01143-0.

Matched-pair analysis of mCRPC patients receiving 177Lu-labeled PSMA-targeted radioligand therapy in a 4-week versus 6-week treatment interval

Amir Karimzadeh #  1   2 , Charlotte-Sophie Hecker #  3 , Matthias M Heck  4 , Robert Tauber  4 , Calogero D'Alessandria  3 , Wolfgang A Weber  3 , Matthias Eiber #  3 , Isabel Rauscher #  3
Affiliations

Matched-pair analysis of mCRPC patients receiving 177Lu-labeled PSMA-targeted radioligand therapy in a 4-week versus 6-week treatment interval

Amir Karimzadeh et al. EJNMMI Res. .

Abstract

Background: The optimal regimen for 177Lu-labeled prostate-specific membrane antigen-targeted radioligand therapy, including treatment intervals, remains under study, with evidence suggesting shorter intervals could benefit patients with high disease volume and rapid progression. This retrospective analysis evaluated treatment toxicity, PSA response, PSA-progression-free survival (PSA-PFS), and overall survival (OS) in matched cohorts of mCRPC patients receiving 177Lu-PSMA-RLT at 4-week versus 6-week intervals.

Results: A PSA response (PSA decline ≥ 50%) was achieved in 47.8% and 21.7% of patients in the 4-week and 6-week treatment interval groups, respectively (p = 0.12). There was a trend towards longer PSA-PFS in the 4-week group compared to the 6-week group (median PSA-PFS, 26.0 weeks vs. 18.0 weeks; HR 0.6; p = 0.2). Although not statistically significant, there was a trend towards shorter OS in the 4-week group compared to the 6-week group (median OS, 15.1 months vs. 18.4 months; HR 1.3; p = 0.5). The 4-week group had a significantly greater decrease in leucocyte and platelet counts compared to the 6-week group (38.5% vs. 18.2% and 26.7% vs. 10.7%; p = 0.047 and p = 0.02). Severe adverse events were modest in both groups.

Conclusions: Intensifying treatment intervals from 6 weeks to 4 weeks showed some improvements in PSA response and PSA-PFS for mCRPC patients, but did not significantly affect OS. Additionally, bone marrow reserve was significantly reduced with the intensified regimen. Therefore, the overall benefit remains uncertain, and further prospective studies are needed to compare 4-week and 6-week intervals regarding toxicity, treatment response, and outcome.

Keywords: 4-week treatment interval; Metastatic castration-resistant prostate cancer (mCRPC); Prostate-specific membrane antigen (PSMA); Radioligand therapy (RLT).

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Conflict of interest statement

IR&ME report fees from Blue Earth Diagnostics Ltd. (consultant, research funding). IR is an Associate Editor of EJNMMI Research. ME reports fees from Novartis/AAA (consultant, speaker), Telix (consultant), Bayer (consultant, research funding), RayzeBio (consultant), Point Biopharma (consultant), Eckert-Ziegler (speaker), ABX GmbH (speaker) and Janssen Pharmaceuticals (consultant, speakers bureau), Parexel (image review) and Bioclinica (image review) outside the submitted work and a patent application for rhPSMA. He and other inventors are entitled to royalties on sales of POSLUMA®. RT: Advisory boards, speaking fees; travel support, conference access; author fees; shares: Astellas, AstraZeneca, Bayer, BMS, Eisai, EUSA, Ipsen, Janssen, Merck, MSD, Novartis, Orion, Philogen, Roche, Sanofi, Thieme. No other potential conflicts of interest relevant to this article exist.

Figures

Fig. 1
Fig. 1
Treatment scheme in the 4-week and 6-week interval groups. Asterisks indicate deviations from the 4-week and 6-week treatment intervals, given as median (range), due to individual delays in conducting the first interim PSMA-ligand PET/CT
Fig. 2
Fig. 2
Relative changes in lab values. Creatinine, haemoglobin, leukocyte, and platelet counts at the last available cycle of [177Lu]Lu-PSMA-I&T, comparing patients treated every 4 weeks (red) to those treated every 6 weeks (green). A significant p-value relative to baseline is indicated as * (< 0.05). Data are represented as median values, with their ranges in brackets
Fig. 3
Fig. 3
Adverse events based on CTCAE v. 5.0. Adverse events based on CTCAE v. 5.0 for haemoglobin, leukocytes, platelets, and creatinine were compared in percentages between patients undergoing 4-week (red) and 6-week (green) treatment intervals, both at baseline and the final treatment cycle. Grade ≥ III toxicities are indicated by horizontal lines. From baseline, in the 4-week treatment interval group, there were two instances of grade III anemia and one of grade III leukopenia. In the 6-week treatment interval group, one grade III anemia and one grade III thrombocytopenia were observed; however, the same patient already had grade III anemia at baseline. There were no other grade III/IV toxicities in either group
Fig. 4
Fig. 4
Best PSA response as relative changes from baseline. Best PSA response in patients treated every 4 weeks (red) compared to those treated every 6 weeks (green). Data are represented as median values, with their ranges in brackets. Waterfall plot showing response to treatment as measured by serum PSA. Best PSA response, defined as the smallest increase or greatest decrease in PSA from baseline in patients with 4-week treatment interval (red) and 6-week treatment interval (green). Asterics indicate patients with an increase of > 100% as the best PSA response
Fig. 5
Fig. 5
Kaplan-Meier survival curves. PSA-progresion-free survival and overall survival stratified by patients receiving treatment every 4 (red) and 6 weeks (green)
See this image and copyright information in PMC

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