Blood-based tumor mutational burden impacts clinical outcomes of immune checkpoint inhibitor treated breast and prostate cancers.
Autor: | Barnett RM; Guardant Health, Inc, Palo Alto, California, USA., Jang A; University Hospitals Seidman Cancer Center, Cleveland, OH, USA.; Tulane Cancer Center, New Orleans, LA, USA., Lanka S; Tulane Cancer Center, New Orleans, LA, USA., Fu P; University Hospitals Seidman Cancer Center, Cleveland, OH, USA., Bucheit LA; Guardant Health, Inc, Palo Alto, California, USA., Babiker H; Mayo Clinic Jacksonville, Jacksonville, FL, USA., Bryce A; Mayo Clinic Phoenix, Phoenix, AZ, USA., Meyer HM; Mayo Clinic Phoenix, Phoenix, AZ, USA., Choi Y; Emory University, Atlanta, GA, USA., Moore C; UT Southwestern University, Dallas, TX, USA., Garje R; Miami Cancer Institute Baptist Health, Miami, FL, USA., Gao X; Massachuesetts General Hospital Cancer Center, Boston, MA, USA., Kim DW; Moffitt Cancer Institute, Tampa, FL, USA., Chang RY; University Hospitals Seidman Cancer Center, Cleveland, OH, USA., Gulhati P; Rutgers University, New Brunswick, NJ, USA., Ramaker R; Mayo Clinic, Rochester, MN, USA., Bansal R; Mayo Clinic, Rochester, MN, USA., Zhang T; UT Southwestern University, Dallas, TX, USA., Oliver Sartor A; Mayo Clinic, Rochester, MN, USA., Armstrong AJ; Duke Cancer Institute Center for Prostate and Urologic Cancers, Duke University, Durham, NC, USA., Bilen MA; Emory University, Atlanta, GA, USA., Barata P; University Hospitals Seidman Cancer Center, Cleveland, OH, USA. Pedro.Barata@UHhospitals.org.; Tulane Cancer Center, New Orleans, LA, USA. Pedro.Barata@UHhospitals.org. |
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Jazyk: | angličtina |
Zdroj: | Communications medicine [Commun Med (Lond)] 2024 Dec 02; Vol. 4 (1), pp. 256. Date of Electronic Publication: 2024 Dec 02. |
DOI: | 10.1038/s43856-024-00687-5 |
Abstrakt: | Background: Breast and prostate tumors are known to be less responsive to immune checkpoint inhibitors (ICIs). Tissue-based tumor mutation burden (tTMB) has emerged as a predictive biomarker of response to ICIs, including in these "cold tumors". In clinical practice, when tTMB is not available, blood-based TMB score (bTMB) can be used to consider treatment with ICIs. Methods: This retrospective, real-world study included a final cohort of metastatic breast and prostate cancer patients treated with an ICI following a liquid biopsy test. Multiple bTMB-High cut-offs were assessed. Clinical, genomic, and outcomes data were collected. We hypothesized that a cut-off of bTMB ≥10 mut/Mb is not a strong predictor of response to ICIs in this setting. The Guardant Health genomic database (GHGD) was then queried (N = 13,992) for associations of bTMB with genomic alterations. Results: In the clinical cohort (N = 48), ICI treatment is offered after a median of 3 (1-9) lines of treatment. The median bTMB is 16.4 (10-186) mut/Mb. The median time on ICI and PFS is 2.1 (0-1.7) and 3.1 months (95%CI, 1.6-4.6) respectively; no difference by MSI/MMR status (p = 0.152). Response rate among eligible patients (n = 36) is 16.7%; only N = 1/6 in bTMB <16 mut/Mb. High bMSI is associated with higher bTMB (correlation test, r = 0.66, p = 0.000). In the GHGD, patients with bTMB high have significantly more alterations than bTMB low and TP53, PIK3CA, ATM, ESR1, NF1, BRCA2, ARID1A, and APC were the most frequently altered genes. Conclusions: In this study, the practice of offering an ICIs based on bTMB was uncommon and did not independently predict ICI benefits in patients with refractory, advanced breast and prostate cancers. Competing Interests: Competing interests: R.M.B. and L.A.B. are employees and stockholders of Guardant Health. All other authors have no competing interests pertaining to this study. (© 2024. The Author(s).) |
Databáze: | MEDLINE |
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