Atezolizumab in platinum-treated locally advanced or metastatic urothelial carcinoma: post-progression outcomes from the phase II IMvigor210 study

Abstract

Background: Conventional criteria for tumor progression may not fully reflect the clinical benefit of immunotherapy or appropriately guide treatment decisions. The phase II IMvigor210 study demonstrated the efficacy and safety of atezolizumab, a programmed death-ligand 1-directed antibody, in patients with platinum-treated locally advanced or metastatic urothelial carcinoma. Patients could continue atezolizumab beyond Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 progression at the investigator's discretion: this analysis assessed post-progression outcomes in these patients.

Patients and methods: Patients were treated with atezolizumab 1200 mg i.v. every 3 weeks until loss of clinical benefit. Efficacy and safety outcomes in patients who experienced RECIST v1.1 progression and did, or did not, continue atezolizumab were analyzed descriptively.

Results: In total, 220 patients who experienced progression from the overall cohort (n = 310) were analyzed: 137 continued atezolizumab for ≥ 1 dose after progression, 19 received other systemic therapy, and 64 received no further systemic therapy. Compared with those who discontinued, patients continuing atezolizumab beyond progression were more likely to have had a baseline Eastern Cooperative Oncology Group performance status of 0 (43.1% versus 31.3%), less likely to have had baseline liver metastases (27.0% versus 41.0%), and more likely to have had an initial response to atezolizumab (responses in 11.7% versus 1.2%). Five patients (3.6%) continuing atezolizumab after progression had subsequent responses compared with baseline measurements. Median post-progression overall survival was 8.6 months in patients continuing atezolizumab, 6.8 months in those receiving another treatment, and 1.2 months in those receiving no further treatment. Atezolizumab exposure-adjusted adverse event frequencies were generally similar before and following progression.

Conclusion: In this single-arm study, patients who continued atezolizumab beyond RECIST v1.1 progression derived prolonged clinical benefit without additional safety signals. Identification of patients most likely to benefit from atezolizumab beyond progression remains an important challenge in the management of metastatic urothelial carcinoma.

Clinicaltrials.gov id: NCT02108652.

Keywords: PD-L1; atezolizumab; immunotherapy; post-progression outcomes; programmed death-ligand 1; urothelial cancer.

© The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Figures

Figure 1.

Changes in sum of target lesion longest diameters (SLDs) on study. (A) Changes in SLDs from the start of treatment in patients treated with atezolizumab, after Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST v1.1) progression, who achieved a confirmed objective response before RECIST v1.1 progression [per independent review facility assessment (IRF)] (n = 16) The first occurrence of IRF-assessed PD is indicated by red circles. (B) Best post-progressive disease (PD) change in SLDs (from time of PD) for all patients treated with atezolizumab post-PD and who had a post-PD evaluation (n = 108). Response status refers to best overall post-PD response (per IRF) relative to study baseline. CR, complete response; PR, partial response; SD, stable disease.

Figure 2.

Overall survival (OS) from time of progression. Kaplan–Meier plot of OS by treatment status beyond progression. Inset displays median post-progression OS and 12-month OS rates. Median post-progression survival follow-up durations were 17.3 months (range, 0.2+ to 21.0 months) in patients who received atezolizumab beyond progression 15.0 months (range, 1.0+ to 16.7 months) in patients who received other systemic therapy, and not estimable (range, 0-11.5+ months) in patients who received no systemic therapy beyond progression.