Atezolizumab in patients with renal insufficiency and mixed variant histology: analyses from an expanded access program in platinum-treated locally advanced or metastatic urothelial carcinoma.

BACKGROUND

Atezolizumab is a treatment for locally advanced/metastatic urothelial carcinoma (mUC). However, its use in patients with renal insufficiency or UC with mixed variant histology (MVH) is not well characterized.

OBJECTIVE

To report efficacy and safety of atezolizumab in these special subpopulations from an expanded access program (EAP).

DESIGN, SETTING, AND PARTICIPANTS

A total of 218 patients were enrolled at 36 US study sites (November 2015-August 2016), and the trial ended following the approval of atezolizumab by the US Food and Drug Administration. This post hoc analysis investigated outcomes in specific study subgroups.

INTERVENTION

Atezolizumab 1200 mg was administered intravenously every 3 weeks until loss of clinical benefit, unacceptable toxicity, death, consent withdrawal, decision to discontinue, commercial availability, or study closure.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS

Response Evaluation Criteria in Solid Tumors V.1.1 responses and safety were evaluated by baseline renal function and histology.

RESULTS AND LIMITATIONS

Objective responses occurred in 0/6 (0%), 4/19 (21%), 1/27 (3.7%), and 12/62 (19%) of evaluable patients with creatinine clearance (CrCl) <30, 30-45, 45-60, and ≥60 mL/min, respectively, and stable disease was seen in three patients with CrCl <30 mL/min. Objective responses were seen in 13/102 patients (13%) with urothelial carcinoma (UC) histology only and in 4/12 patients (33%) with UC with MVH. Treatment-related adverse event frequencies ranged from 35% to 54% across the earlier indicated CrCl subgroups and they were also similar in patients with pure UC or UC with MVH (46%).

CONCLUSIONS

In this EAP mUC subgroup analysis, clinical benefit of atezolizumab occurred in patients with compromised renal function or MVH UC tumors. Safety was comparable across subgroups.

PATIENT SUMMARY

We examined the efficacy and safety of atezolizumab for UC in certain patients participating in an EAP. We found that responses to atezolizumab occurred, and safety was similar, in most patient subgroups with varying levels of kidney functioning or less common types of tumor tissue histology.

Informations de copyright

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Déclaration de conflit d'intérêts

Competing interests: JHC certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: All authors report funding of editorial support from F. Hoffmann-La Roche, Ltd. JHC has received consultancy fees from Foundation Medicine and AstraZeneca. SP has received consulting fees from Astellas, Aveo, Bristol-Myers Squibb, Eisai, Exelixis, Genentech, Ipsen, Novartis, F. Hoffman-La Roche, Ltd and Pfizer. CK and BD are employed by and own stock in Genentech. JB has received research support and grants from Pfizer; has received consulting fees and honoraria from Bristol-Myers Squibb, Genentech, Merck, Pierre Fabre, and AstraZeneca; has received royalties from UptoDate bladder.