Lutetium 177 Therapy Success Impacted by Prognostic Risk Group, Receipt of Subsequent Therapies in mCRPC

Overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC) who are receiving lutetium 177 (177Lu) may be impacted by Cancer and Leukemia Group B (CALGB) prognostic risk group and the receipt of subsequent FDA-approved life-prolonging therapies, according to data from a combined prognostic factor analysis presented during the 2021 AUA Annual Meeting.

The overall median OS observed with 177Lu was 20.7 months (95% CI, 17.4-24.0) in 125 patients with mCRPC who received treatment on sequential prospective clinical trials of the prostate-specific membrane antigen (PSMA)–targeted beta-emitting radionuclide. The median OS in those who received 177Lu-J591 (n = 76) was slightly longer, at 23.3 months (95% CI, 21.1-32.6). In those who received 177Lu-PSMA-617 (n = 49), the median OS was 16.7 months (95% CI, 10.9-20.7).

Factors linked with longer OS included CALGB prognostic score (28.1 months vs 16.9 months; P < .0001), circulating tumor cell (CTC) decline (24.9 months vs 19.2 months; P = .046), and receipt of subsequent therapy (28.1 months vs 14.8 months; P = .0002).

Moreover, higher PSMA PET standardized uptake value (SUV; imaging score 4 vs 0 to 3) was linked with prolonged OS (18 months vs 10 months; P = .015), and higher administered activity (22.1 months vs 18.6 months; P = .074) and DNA damage repair (DDR) alterations (33.9 months vs 20.6 months; P = .24) tended to be associated with longer OS.

“DDR mutations, higher administered radioactivity, higher PSMA PET SUV, and posttreatment [circulating tumor cell] count decline are promising biomarkers worthy of further exploration,” Scott Tagawa, MD, MS, FACP, study author, professor of medicine and urology at Weill Cornell Medicine, and an attending physician at NewYork-Presbyterian–Weill Cornell Medical Center, said in a poster presentation on the data.

PSMA-targeted radionuclide therapy represents a promising treatment for patients with advanced prostate cancer, Tagawa said. PSMA can be targeted using antibodies, such as J591, or small molecule ligands, like PSMA-617, labeled with 177Lu. However, optimal selection and effective biomarkers still need to be defined and established, Tagawa added.

To conduct the combined prognostic analysis presented during the meeting, investigators collected data from a total of 125 patients who received treatment with 177Lu on prospective PSMA-TRT clinical trials at a single institution between 2003 and 2020. To be included in the analysis, patients had to have completed treatment with the radionuclide therapy at least 1 year before the analysis.

Variables of interest included type of PSMA targeting, dose administered, comorbidities, CALGB prognostic risk group, PSMA imaging, CTC counts, known DDR alterations, and receipt of subsequent therapies. PSMA imaging was scored based on the maximum tumor uptake relative to the mean liver uptake on a scale that ranged from 0 to 4. Investigators utilized Cox regression analysis and the Kaplan-Meier method to examine the link between the variables and survival. The data cutoff for the combined analysis was March 2021.

Among the 125 patients included, the median PSA was 50.14 ng/dL (range, 0.66-2222.4) and the median age at treatment was 72 years (range, 48-93). Regarding Halabi risk category, 57.6% of patients had high risk, 37.6% had intermediate risk, and 4.8% had low risk. Additionally, 49.6% previously received taxane chemotherapy and 47.2% previously received abiraterone acetate (Zytiga)/enzalutamide (Erleada). Eighty percent of patients had metastasis in the lymph node, 24.8% in the liver, 24.8% in the lung, and 97.6% in the bone.

The median number of subsequent therapies received was 1 (range, 0-10), and these included abiraterone/enzalutamide (26.4%), docetaxel (32.8%), cabazitaxel (Jevtana; 18.4%), platinum chemotherapy (17.6%), radium-223 dichloride (Xofigo; 7.2%), sipuleucel-T (Provenge; 4.8%), and additional PSMA-TRT (11.2%).

Additional data from a multivariable analysis indicated that high Halabi risk group (HR, 1.78; 95% CI, 1.16-2.73; P = .009) and total number of subsequent therapies (HR, 0.79; 95% CI, 0.71-0.89; P < .001) retained their prognostic significance. Moreover, a trend for DDR mutations holding prognostic significance was observed (HR, 0.68; 95% CI, 0.34-1.36; P = .30).

_Reference

_{Sun M, Thomas C, Ho B, et al. Long-term follow-up and prognostic factor analysis in men with metastatic castration-resistant prostate cancer (mCRPC) who receive prostate-specific membrane antigen (PSMA)-targeted lutetium-177 (177Lu). Presented at: 2021 American Urological Association Annual Meeting; September 10-13, 2021; virtual. Abstract MP24-05.}