medwireNews: Atezolizumab does not significantly improve survival over chemotherapy in patients with platinum-refractory metastatic urothelial carcinoma overexpressing programmed cell death ligand 1 (PD-L1), phase III study data show.
However, patients receiving atezolizumab had fewer adverse events compared with chemotherapy, and exploratory analyses of the intention-to-treat (ITT) population showed durable responses in line with previous phase II data for atezolizumab in this setting.
“[I]n view of the high unmet need in this population, the well tolerated, durable remissions observed with atezolizumab, and the complications associated with chemotherapy, the benefit–risk ratio for atezolizumab can be considered favourable for patients with metastatic urothelial carcinoma previously treated with platinum-containing regimens,” Thomas Powles (Queen Mary University of London, UK) and co-authors remark.
For the IMvigor211 trial, the researchers randomly assigned adults (aged ≥18 years) with metastatic urothelial carcinoma who had progressed after platinum-based chemotherapy to receive atezolizumab 1200 mg (n=467) or the physician’s choice of chemotherapy (vinflunine, paclitaxel, or docetaxel; n=464) intravenously every 3 weeks.
Randomization and data analysis were stratified by PD-L1 expression on tumor-infiltrating immune cells, chemotherapy type (vinflunine vs taxanes), and the presence of liver metastases.
The first stage of the analysis, in the IC2/3 population (defined as PD-L1 expression on 5% or more of tumor-infiltrating immune cells; n=234), showed no significant difference in overall survival (OS) between the patients receiving atezolizumab and those receiving chemotherapy, at a median of 11.1 versus 10.6 months, respectively.
This lack of difference precluded further formal statistical analysis, as per the study protocol, but exploratory analyses in the ITT population showed that median OS was numerically higher with atezolizumab than with chemotherapy, at 8.6 versus 8.0 months.
Confirmed objective response rates were similar between treatment groups in the IC2/3 population, at 23% and 22% with atezolizumab and chemotherapy, respectively, but median duration of response was numerically longer in the IC2/3 atezolizumab group than in the chemotherapy group (15.9 vs 8.3 months).
Atezolizumab was also associated with lower rates of adverse events leading to treatment discontinuation (7 vs 18%) and fewer grade 3–4 treatment-related adverse events (20 vs 43%) than chemotherapy in the ITT population.
Interestingly, Powles and team found that OS and objective response rates were both higher in the IC2/3 population than in the ITT population, regardless of treatment type, which they say negates the potentially predictive effects of PD-L1.
“These results underscore the risks of biomarker-focused statistical designs without supportive randomised data, and highlight the need for improved predictive biomarkers for cancer immunotherapy,” the authors write in The Lancet.
By Laura Cowen
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