Immune Checkpoint Inhibitors vs Chemotherapy for Metastatic, Castration-Resistant Prostate Cancer

Among patients with metastatic, castration-resistant prostate cancer (mCRPC) and high tumor mutational burden (TMB), those treated with immune checkpoint inhibitors (ICIs) experienced longer overall survival (OS) and time to their next treatment (TTNT) compared to those treated with taxanes, according to a comparative-effectiveness analysis. However, those with low TMB, did worse.

“Unfortunately, for patients with…(mCRPC) the objective response rate for ICI treatments has been reported as 3% for patients with tumors without programmed cell death ligand 1 (PD-L1) expression and 5% for those with PD-L1–expressing tumors. For this reason, interest has developed in other biomarkers that might identify patients with mCRPC likely to receive greater clinical benefit from ICIs than alternate treatments[,]” wrote lead author Ryon Graf, PhD, Foundation Medicine, Cambridge, Massachusetts, and coauthors.

Researchers analyzed prospectively defined, biomarker-stratified genomic data contained in a deidentified genomic database regarding 741 men treated at approximately 280 US academic or community-based cancer clinics between January 2011 and April 2021. The data were analyzed between July and August 2021.

Among all 741 patients, 5.9% had TMB of 10 mutations per megabase (mt/Mb) or greater, while 3% had high microsatellite instability, and 2.7% had both.

At baseline, the median (IQR) PSA level was 79.4 (19 to 254) ng/mL, 108 men (18.8%) had Eastern Cooperative Oncology Group Performance Status scores of 2 or greater, and 644 men (86.9%) had received prior systemic treatments for mCRPC.

Of the cohort, 93.9% received taxane treatment, while 6.1% received ICI therapy. Among patients with TMB of 10 mt/Mb or greater, use of ICIs, compared with use taxanes, was associated with more favorable TTNT (median [IQR], 8 [3.4 to unknown] months vs 2.4 [2.4 to 7.3] months; hazard ratio [HR], 0.37, 95% CI, 0.15 to 0.87; P = .02). OS was also significantly higher among such patients (median 19.9 [8.06 to unknown] months vs 4.2 [2.69 to 6.12] months; HR, 0.23; 95% CI, 0.10 to 0.57; P = .001).

However, those patients with TMB of fewer than 10 mt/Mb who received ICIs actually did worse than those who received taxanes (TTNT: 2.4 [1.1 to 3.2] months vs 4.1 [2.2 to 6.3] months; HR, 2.65; 95% CI, 1.78 to 3.95; P <.001).

Source:
Graf R, Fisher V, Weberpals J, et al. Comparative Effectiveness of Immune Checkpoint Inhibitors vs Chemotherapy by Tumor Mutational Burden in Metastatic Castration-Resistant Prostate Cancer. JAMA Netw Open. 2022 Mar 1;5(3):e225394. doi:10.1001/jamanetworkopen.2022.5394.