RECIP 1.0 + PSA for response assessment in mCRPC patients treated with 225Ac / 177Lu PSMA combination therapy
Gabriel T. Sheikh, Astrid Delker, Mathias J. Zacherl, Adrien Holzgreve, Sarah L. Takayama Fouladgar, Marcus Unterrainer, Johannes Rübenthaler, Jozefina Casuscelli, Andrei Gafita, Lena M. Unterrainer
Abstract
Abstract Background Targeted alpha therapy (TAT) with 225 Ac has shown promising results in metastatic castration-resistant prostate cancer (mCRPC) patients pre-treated with [ 177 Lu]Lu-PSMA radioligand therapy (RLT). A combination treatment regimen adding 177 Lu to decreased 225 Ac activities may improve toxicity profile while maintaining sufficient anti-tumor effect. We therefore evaluated clinical and image-based response parameters in patients treated with 225 Ac-/ 177 Lu-PSMA combination therapies (ALCT). Results Complete response (RECIP-CR), partial response (RECIP-PR), stable disease (RECIP-SD), progressive disease (RECIP-PD) according to RECIP 1.0 was observed in 0/25 (0%), 12/25 (48%), 9/25 (36%) and 4/25 (16%) patients, respectively. Response by RECIP + PSA was observed in 14/25 (56%) patients and progression by RECIP + PSA in 8/25 (32%) patients. Interrater reliability for visual RECIP was substantial (κ = 0.757, p < 0.001), while agreement between visual and quantitative RECIP was almost fully congruent (κ = 0.879, p < 0.001). OS did not significantly vary among the four different therapy regimens ( p > 0.05). When grouping patients with declining / stable PSA as responders, these patients showed no significant difference in overall survival compared to patients with progressive PSA after ALCT ( p = 0.312). Similarly, there was no significant difference in median overall survival between patients without RECIP-progression (RECIP-PR + RECIP-SD) and patients with RECIP-progression (RECIP-PD) ( p > 0.05), but when applying the composite classification, RECIP + PSA responders survived significantly longer compared to patients with RECIP + PSA progression ( p = 0.049). Conclusions ALCT is a promising therapeutic regimen that may prolong survival in patients who progress during [ 177 Lu]Lu-PSMA RLT. Our results motivate to further investigate the use of RECIP + PSA as tool for response assessment and for overall survival prediction in mCRPC under ALCT.