Early Responses Observed With Lu-PSMA Administration May Provide Prognostic Outlook in mCRPC

Prostate-specific antigen (PSA) changes were observed 6 weeks after the administration of ¹⁷⁷Lu-PSMA in men with metastatic castration-resistant prostate cancer (mCRPC), suggesting a prognostic value for long-term clinical benefit, according to a single center retrospective analysis presented at the Society of Nuclear Medicine and MolecularImaging 2020 Annual Meeting–Virtual Edition, held from July 11 to 14.

Lead author Andrei Gafi ta, MD, of the Department of Nuclear Medicine, Klinikum Rechts der Isar, Technical University of Munich in Germany, and colleagues wrote in their poster that the earlier response observed in this study could help clinicians decide if a change in treatment is required in the absence of a response. Further, the investigators noted that PSA responses at 6 weeks post treatment could indicate a long-term benefi t for overall survival (OS) and imaging-based progression- free survival (PFS).

A total of 115 men had PSA levels measured at baseline, after 6 weeks of treatment, and at 12 weeks after ¹⁷⁷Lu-PSMA initiation. The percentage change from baseline at 6 and 12 weeks were categorized as a response, progression, and stable. Coprimary end points were OS and PFS. Secondary end points were PSA changes at 12 weeks and PSA flare-up, defined as an increase of at least 25% at 6 weeks followed by a decline below baseline levels at 12 weeks.

The investigators reported that median OS was 13.4 months (95% CI, 11.1-15.6) and the median PFS was 3.3 months (95% CI, 2.0-4.6). Overall, they noted that 50 patients (40%) experienced a PSA decline of greater than 30% at 6 weeks, whereas 30 patients (23%) had a PSA decline of greater than 50%. In the progression group, 3% of patients (1 of 36) had a PSA decline below baseline levels at 12 weeks, suggesting that minimal flare-up was experienced by patients.

Regarding changes to PSA, the investigators noted an association between PSA changes at 6 weeks and 12 weeks, and signifi cance between the percentage changes of those 2 time points (P < .001). Ninety-four percent of 31 patients who exhibited progression at 6 weeks had PSA measurements at 12 weeks (TABLE).

Gafita and colleagues reported that the PSA decline of 30% or greater at 6 weeks was associated with longer OS (median, 16.7 months) compared with both stable PSA (median, 11.8 months; P = .007) and PSA progression (median, 6.5 months; P < .001). PSA decline of 50% or greater at 6 weeks (median, 19.4 months) was not signifi cantly associated with longer OS compared with stable PSA (median, 12.6 months; P = .05), and in contrast to PSA progression (median, 6.5 months; P < .001).

The investigators observed that a PSA decline of 30% or greater at 6 weeks was associated with longer PFS (median, 7.1 months) compared with stable PSA (median, 2.0 months; P = .01) and PSA progression (median, 1.2 months; P <.001). A PSA decline of 50% or greater at 6 weeks was not statistically associated with longer PFS (median, 7.1 months) compared with stable PSA (median, 3.6 months; P = .30), in contrast to PSA progression (median, 1.2 months; P <.001).

The investigators reported that patients with a PSA response at 6 weeks also had a reduced risk of radiographic progression compared with those with stable PSA (HR, 0.60; 95% CI, 0.38-0.94; P = .02), whereas patients with PSA progression had a higher risk of radiographic progression compared with those showing stable PSA (HR, 3.18; 95% CI, 1.95-5.21; P < .001).

The investigators concluded that “PSA measurements as early as 6 weeks after ¹⁷⁷LuPSMA initiation are associated with the clinical outcome and should be further investigated as a surrogate end point for clinical trials. Patient [treatment] decisions and…PSA flare-up during ¹⁷⁷LuPSMA treatment is uncommon.”

_Reference:

_{Gafi ta A, Heck M, Rauscher I, et al. Early prostate-specifi c antigen changes and clinical outcome following 177Lu-PSMA radionuclide treatment in patients with metastatic castration-resistant prostate cancer. J Nucl Med. 2020:61(suppl 1):591. doi:10.2967/jnumed.119.240242}