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Updated Overall Survival by Circulating Tumor DNA Status from the Phase 3 IMvigor010 Trial: Adjuvant Atezolizumab Versus Observation in Muscle-invasive Urothelial Carcinoma.
- Source :
-
European urology [Eur Urol] 2024 Feb; Vol. 85 (2), pp. 114-122. Date of Electronic Publication: 2023 Jul 26. - Publication Year :
- 2024
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Abstract
- Background: Interim results from IMvigor010 showed an overall survival (OS) benefit for adjuvant atezolizumab (anti-PD-L1) versus observation in patients with circulating tumor DNA (ctDNA)-positive muscle-invasive urothelial carcinoma (MIUC).<br />Objective: To report updated OS and safety by ctDNA status.<br />Design, Setting, and Participants: This ad hoc analysis from a global, open-label, randomized, phase 3 trial (NCT02450331) included intention-to-treat (ITT) population with evaluable cycle 1 day 1 (C1D1) ctDNA samples.<br />Intervention: Atezolizumab (1200 mg every 3 wk) or observation for ≤1 yr.<br />Outcome Measurements and Statistical Analysis: OS, relapse rates, and safety by ctDNA status were assessed.<br />Results and Limitations: Among 581 of 809 ITT patients included, 214 (37%) were ctDNA positive. Atezolizumab did not improve OS versus observation in ITT patients (hazard ratio [HR] 0.91 [95% confidence interval {CI} 0.73-1.13]; median follow-up 46.8 mo [interquartile range, 36.1-53.6]). In the observation arm, ctDNA positivity versus negativity was associated with shorter OS (HR 6.3 [95% CI 4.3-9.3]). The ctDNA positivity identified patients with an OS benefit favoring atezolizumab versus observation (HR 0.59 [95% CI 0.42-0.83]). A greater reduction in ctDNA levels with atezolizumab (C3D1) was associated with longer OS (100% clearance, 60.0 mo [95% CI 35.5-not estimable]; 50-99% reduction, 34.3 mo [95% CI 15.2-not estimable]; <50% reduction, 19.9 mo [95% CI 16.4-32.2]). The ctDNA positivity at C1D1 + C3D1 was associated with relapse with greater sensitivity than C1D1 alone (68% vs 57%). Adverse events were more frequent with atezolizumab than with observation, regardless of ctDNA status. A study limitation was its exploratory design.<br />Conclusions: Evidence suggests that ctDNA positivity in MIUC predicts a benefit with atezolizumab. An in-progress prospective study will further evaluate these findings.<br />Patient Summary: Among patients with urothelial cancer after surgery, survival was poorer if tumor-derived DNA was detected in their bloodstream; these patients' survival was longer with atezolizumab versus observation. Bloodstream tumor-derived DNA may identify patients who benefit from atezolizumab.<br /> (Copyright © 2023. Published by Elsevier B.V.)
- Subjects :
- Humans
Prospective Studies
Treatment Outcome
Neoplasm Recurrence, Local
Adjuvants, Immunologic therapeutic use
Muscles pathology
Recurrence
Antineoplastic Combined Chemotherapy Protocols
Carcinoma, Transitional Cell drug therapy
Carcinoma, Transitional Cell genetics
Carcinoma, Transitional Cell pathology
Circulating Tumor DNA genetics
Urinary Bladder Neoplasms
Antibodies, Monoclonal, Humanized
Subjects
Details
- Language :
- English
- ISSN :
- 1873-7560
- Volume :
- 85
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- European urology
- Publication Type :
- Academic Journal
- Accession number :
- 37500339
- Full Text :
- https://doi.org/10.1016/j.eururo.2023.06.007