Tumor mutational burden (TMB) may help guide treatment decisions for patients with metastatic castration-resistant prostate cancer (mCRPC), according to a study published in JAMA Oncology.

Researchers found that immune checkpoint inhibitors (ICIs) were more effective than taxanes in patients with mCRPC who had a TMB of 10 mutations per megabase (mt/Mb) or greater.

This finding supports the existing TMB cutoff of 10 mt/Mb for ICI use in later lines of therapy, according to researchers. The results also suggest that ICIs may be a viable alternative to taxane chemotherapy for patients with mCRPC and high TMB.

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This study included 741 patients with mCRPC (median age, 70 years) who were treated between January 2011 and April 2021. All patients underwent genomic profiling and were treated with ICIs or single-agent taxane therapy.

Most patients (93.9%) received taxanes, 6.1% received ICIs, 5.9% had a high TMB (10 mt/Mb or greater), 3.0% had high microsatellite instability, and 2.7% had both high TMB and high microsatellite instability.

Patients with a high TMB had significantly longer time to next treatment (TTNT) and overall survival (OS) with ICIs vs taxanes.

Among patients with a high TMB, the median TTNT was 8.0 months for those treated with ICIs and 2.4 months for those who received taxanes (hazard ratio [HR], 0.37, 95% CI, 0.15-0.87; P =.02). The median OS was 19.9 months and 4.2 months, respectively (HR, 0.23; 95% CI, 0.10-0.57; P =.001).

Among patients without high TMB, TTNT was significantly worse for those who received ICIs. The median TTNT was 2.4 months with ICIs and 4.1 months with taxanes (HR, 2.65; 95% CI, 1.78-3.85; P <.001).

On the other hand, there was no significant difference in OS between the treatment types for patients without high TMB. The median OS was 4.2 months with ICIs and 6.0 months with taxanes (HR, 1.08; 95%CI, 0.68-1.74; P =.73).

The researchers noted that this study is limited because it is not a randomized clinical trial, treatment choice was at the clinician’s discretion, and there were only 45 patients who received ICIs. Still, the researchers said their findings suggest that ICIs are a viable alternative to taxanes for patients with mCRPC and a TMB of 10 mt/Mb or greater.

Disclosures: This research was supported by Foundation Medicine. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Graf RP, 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. Published online March 31, 2022. doi:10.1001/jamanetworkopen.2022.5394