Updated Overall Survival by Circulating Tumor DNA Status from the Phase 3 IMvigor010 Trial: Adjuvant Atezolizumab Versus Observation in Muscle-invasive Urothelial Carcinoma.

Powles, Thomas; Assaf, Zoe June; Degaonkar, Viraj; Grivas, Petros; Hussain, Maha; Oudard, Stephane; Gschwend, Jürgen E; Albers, Peter; Castellano, Daniel; Nishiyama, Hiroyuki; Daneshmand, Siamak; Sharma, Shruti; Sethi, Himanshu; Aleshin, Alexey; Shi, Yi; Davarpanah, Nicole; Carter, Corey; Bellmunt, Joaquim; Mariathasan, Sanjeev

doi:10.1016/j.eururo.2023.06.007

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Title:: Updated Overall Survival by Circulating Tumor DNA Status from the Phase 3 IMvigor010 Trial: Adjuvant Atezolizumab Versus Observation in Muscle-invasive Urothelial Carcinoma.
Document type:: Article; Journal Article
Author(s):: Powles, Thomas; Assaf, Zoe June; Degaonkar, Viraj; Grivas, Petros; Hussain, Maha; Oudard, Stephane; Gschwend, Jürgen E; Albers, Peter; Castellano, Daniel; Nishiyama, Hiroyuki; Daneshmand, Siamak; Sharma, Shruti; Sethi, Himanshu; Aleshin, Alexey; Shi, Yi; Davarpanah, Nicole; Carter, Corey; Bellmunt, Joaquim; Mariathasan, Sanjeev
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). OBJECTIVE: To report updated OS and safety by ctDNA status. 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. INTERVENTION: Atezolizumab (1200 mg every 3 wk) or observation for ≤1 yr. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: OS, relapse rates, and safety by ctDNA status were assessed. 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. CONCLUSIONS: Evidence suggests that ctDNA positivity in MIUC predicts a benefit with atezolizumab. An in-progress prospective study will further evaluate these findings. 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.
Journal title abbreviation:: Eur Urol
Year:: 2024
Journal volume:: 85
Journal issue:: 2
Pages contribution:: 114-122
Fulltext / DOI:: doi:10.1016/j.eururo.2023.06.007
Pubmed ID:: http://view.ncbi.nlm.nih.gov/pubmed/37500339
Print-ISSN:: 0302-2838
TUM Institution:: Klinik und Poliklinik für Urologie (Prof. Gschwend)
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mediaTUM Gesamtbestand Einrichtungen Schools TUM School of Medicine and Health Departments Clinical Medicine Klinik und Poliklinik für Urologie (Prof. Gschwend)2024