The IMvigor010 study (NCT02450331) compared adjuvant atezolizumab with observation in patients with post-operative muscle-invasive urothelial carcinoma (n=809). No significant difference in disease-free survival was reported between participants in the atezolizumab group and those in the observation group. However, an exploratory analysis did indicate that ctDNA-positive patients benefitted from atezolizumab regarding (HR 0.59; 95% CI 0.41–0.86). The updated results of this trial were presented by Prof. Jürgen Gschwend (Technical University Munich, Germany).
After a median follow-up of 36.4 months, the OS of the total study population was still not increased with atezolizumab treatment instead of observation (HR 0.91; 95% CI 0.73–1.13). However, patients with a known ctDNA-positive status (n=214) displayed a significant OS benefit if they had been randomised to the atezolizumab arm (HR 0.59; 95% CI 0.42–0.83), with corresponding median OS results of 29.8 months and 14.1 months for ctDNA-positive patients in the atezolizumab and observation arm, respectively. Prof. Gschwend added that ctDNA-positivity was associated with a worse prognosis than ctDNA-negativity (HR 6.30; 95% CI 4.30–9.30). Furthermore, the effect of atezolizumab on the OS of ctDNA-positive patients appeared to be somewhat more pronounced in patients with PD-L1 expression levels ≥5% (HR 0.51; 95% CI 0.30–0.85) than in those with PD-L1 levels <5% (HR 0.75; 95% CI 0.49–1.16).
Prof. Gschwend emphasised that these results are hypothesis-generating only and that adjuvant atezolizumab is currently being assessed prospectively in ctDNA-positive patients with muscle-invasive urothelial carcinoma in the IMvigor011 trial (NCT04660344).
1. Gschwend JE, et al. Overall survival (OS) by circulating tumor DNA (ctDNA) status in patients with post-operative muscle-invasive urothelial carcinoma (MIUC) treated with atezolizumab (atezo): update from IMvigor010. Game-changing session 5, EAU 2022, 01–04 July.
2. Bellmunt J, et al. Lancet Oncol. 2021;22:525–537.