Adjuvant Girentuximab Fails To Extend Nonmetastatic Clear-Cell RCC Survival

Survival endpoints do not vary significantly between patients with localised clear-cell renal cell carcinoma given girentuximab and those given placebo after undergoing nephrectomy

medwireNews: In patients with localised clear-cell renal cell carcinoma (RCC) at high risk of recurrence, adjuvant treatment with girentuximab does not improve survival relative to placebo, according to the ARISER trial.

The phase III study is the latest to show negative results in the post-nephrectomy setting and “illustrates the difficulty in successful adjuvant RCC therapeutic discovery”, say Karim Chamie, from the David Geffen School of Medicine at UCLA in Los Angeles, California, USA, and fellow investigators in JAMA Oncology.

They enrolled 864 nonmetastatic clear-cell RCC patients at high risk of recurrence after partial or radical nephrectomy, and randomly assigned them to receive either the chimeric carbonic anhydrase IX-directed monoclonal antibody – at a loading dose of 50 mg in the first week, then at 20 mg/week for up to 24 weeks – or placebo.

Disease-free survival (DFS) was comparable for the 433 participants given intravenous girentuximab and the 431 given placebo, at a median of 71.4 months and not reached, respectively (hazard ratio=0.97).

Median overall survival was likewise similar, being not reached in either arm after a median follow-up of 54.1 and 54.0 months for the girentuximab and placebo groups, respectively.

The researchers highlight the “surprisingly long” survival times of the study cohort, noting that these resulted in “a longer-than-expected study duration.”

Writing in a related editorial, Martin Voss and Robert Motzer, from the Memorial Sloan Kettering Cancer Center in New York, USA, observe that this result “reflects that the overall study population was at lower risk than anticipated”, and that the trial was likely underpowered to demonstrate a significant effect.

The editorialists note that DFS varied significantly between the three pathological risk groups, namely, patients with clinically localised (pT1b/pT2Nx/N0M0 nuclear grade ≥3), locally advanced (pT3/pT4Nx/N0M0) or node-positive (pTanyN+M0) disease, with median times of not reached, 71.7 and 2.9 months, respectively.

“This finding raises the concern that patients in the lower-risk groups, particularly those enrolled based on tumor grade with a low T stage, may have diluted a treatment effect for girentuximab vs placebo that one might have appreciated if only looking at higher-risk participants”, they write.

The study authors also raise this point and suggest that “future trials should consider limiting enrollment to only those patients with locally advanced or node-positive disease to ensure an event rate that is sufficiently high to detect a treatment effect.”


Chamie K, Donin NM, Klöpfer P, et al. Adjuvant weekly girentuximab following nephrectomy for high-risk renal cell carcinoma. The ARISER randomized clinical trial. JAMA Oncol; Advance online publication 27 October 2016. doi:10.1001/jamaoncol.2016.4419

Voss MH, Motzer RJ. Perioperative management of localized kidney cancer. Watching and waiting. JAMA Oncol; Advance online publication 27 October 2016. doi:10.1001/jamaoncol.2016.4409

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