AI Article Synopsis
- - The study investigated the relationship between Tumor Mutational Burden (TMB) and Microsatellite Instability (MSI) status in patients with urothelial carcinoma (UC) receiving immune checkpoint inhibitors (ICI), focusing on overall survival (OS).
- - Results showed that patients with a higher TMB (≥10 mut/Mb) generally experienced longer median OS compared to those with lower TMB, although these differences weren't always statistically significant.
- - Notably, patients treated with maintenance avelumab had a significantly better OS when TMB was high (61 months vs. 17 months for low TMB), indicating potential benefits of ICI based on TMB and MSI status, warranting further investigation.
Article Abstract
Background: Microsatellite Instability (MSI) and Tumor Mutational Burden (TMB) are associated with immune checkpoint inhibitor (ICI) efficacy. We examined the association between TMB and MSI status with survival in patients with urothelial carcinoma (UC) treated with ICI.
Methods: Patients from 15 institutions were treated with ICI monotherapy. Primary endpoint was overall survival and secondary endpoints included observed response rate (ORR), and progression-free (PFS) calculated from ICI initiation. TMB was analyzed as dichotomous (≥10 vs. <10 mut/Mb) and continuous variable.
Results: We identified 411 patients: 203 were treated with ICI 1L/upfront; 104 with 2 + L. For the 1L/upfront: median [m] OS was numerically longer in patients with TMB ≥10 versus TMB <10: mOS 35 versus 26 months (HR = 0.6) and with MSI-H and MSI-S (mOS NR vs. 22 months), though neither association was statistically significant. A statistically significant association was found between TMB (continuous variable) and OS (HR = 0.96, P = .01). For 2 + L: mOS was numerically longer in patients with TMB ≥10 versus TMB <10: (20 vs. 12 months; HR = 0.9); mOS was 12 and 17 months for patients with MSI-H and MSI-S, respectively. Eighty-nine patients received maintenance avelumab (mAV): mOS was longer in patients with TMB ≥10 versus TMB <10: 61 versus 17 months; (HR = 0.2, P = .02) and with MSI-H and MSI-S (NR vs. 24 months).
Conclusions: Although not reaching statistical significance in several subsets, patients with high TMB and MSI-H had numerically longer OS with ICI, especially with mAV. Further validation is needed.
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| http://dx.doi.org/10.1016/j.clgc.2024.102198 | DOI Listing |
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