Primary analysis from IMvigor010, adjuvant atezolizumab in high risk muscle-invasive urothelial carcinoma

The randomised, phase 3 IMvigor010 study did not meet its primary endpoint of disease-free survival (DFS) after treatment with adjuvant atezolizumab in patients with muscle-invasive urothelial cancer. Overall survival (OS) follow-up is ongoing. Additional exploratory biomarkers and subgroup analyses may warrant further study.

Radical surgery with or without cisplatin-based neoadjuvant chemotherapy is the current standard-of-care for muscle-invasive urothelial carcinoma. However, there is no conclusive level I evidence for adjuvant chemotherapy value with regard to OS, and only up to 50% of patients are eligible for cisplatin-based chemotherapy. Atezolizumab, an anti-PD-L1 antibody, is indicated as monotherapy in multiple locally advanced or metastatic urothelial carcinoma disease settings.

The IMvigor010 study evaluated the benefit of adjuvant atezolizumab versus observation in patients with high-risk muscle-invasive urothelial carcinoma of the bladder, renal pelvis, or the ureter [1]. Primary endpoint of IMvigor010 was DFS, secondary endpoint was OS. Patients were stratified by important clinical criteria, including number of lymph nodes resected, prior utilisation of neoadjuvant chemotherapy, lymph node status, tumour stage, and PD-L1 status. After stratification, patients were randomised 1:1 to atezolizumab (1,200 mg every 3 weeks for 16 cycles, or 1 year) or observation. There was no crossover allowed. The intention-to-treat population included 809 patients; in more than 90% the bladder was the primary tumour site. About half of the patients had received prior neoadjuvant chemotherapy. The very high-risk profile of the patient population was reflected by their pathologic stage, with patients having pathologic T-3 or T-4 disease in close to 40% of the patients in both arms, and 52% of the patients having node-positive disease.

Median DFS, the primary endpoint of IMvigor010, was 19.4 months in the atezolizumab arm versus 16.6 months in the observation arm. This difference did not translate into a significant hazard ratio (HR 0.89; 95% CI 0.74-1.08; P=0.244). There was no trend in favour of atezolizumab in any clinical or histochemical (PD-L1 expression) prespecified subgroup. OS results are not yet mature.

Overall, atezolizumab treatment was well tolerated. Treatment-related adverse events occurred in 71% of the atezolizumab arm. Treatment-related grade 3 or 4 events occurred in 16% of the patients in the atezolizumab arm. There was one episode of a grade 5 event that was attributed to atezolizumab that occurred in one patient. Adverse events leading to discontinuation of atezolizumab occurred in 16% of the patients.

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   1. Hussain MHA, et al. ASCO Virtual Meeting, 29-31 May 2020, Abstract

Posted on 17 September 202022 February 2024