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Adjuvant girentuximab fails to provide clinical benefit in clear cell renal cell carcinoma
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Adjuvant girentuximab failed to improve DFS or OS in patients with localized, completely resected, high-risk clear cell renal cell carcinoma, according to results from the ARISER trial.
Up to 30% of patients who present with renal cell carcinoma will develop disease recurrence during follow-up of surgical resection. Most recurrences occur within 5 years, Karim Chamie, MD, MSHS, assistant professor-in-residence of urology at UCLA, and colleagues wrote.
However, no clinically proven adjuvant therapies are available for this patient population.
“Carbonic anhydrase IX (CAIX) is a cell surface glycoprotein member of the carbonic anhydrase family and is expressed in approximately 95% of clear cell renal cell carcinoma (ccRCC) but is absent from normal kidney and minimally expressed in nonrenal tissues and is, thus, an attractive potential target for the diagnosis and treatment of patients with ccRCC,” the researchers added.
Phase 2 trials of girentuximab (Rencarex, Wilex) — a chimeric monoclonal antibody that binds CAIX — in metastatic renal cell carcinoma suggested the drug may slow disease progression.
Researchers of the ARISER trial evaluated the safety and efficacy of adjuvant girentuximab in 864 patients (66% male; median age, 58) with localized, completely resected, high-risk ccRCC.
The researchers randomly assigned patients 433 to receive a single 50-mg loading dose of girentuximab in week 1 of treatment followed by weekly 20-mg IV infusions during weeks 2 through 24. The other 431 patients received placebo.
Patients in the girentuximab arm and placebo arm demonstrated similar 5-year DFS (53.9% vs. 51.6%; HR = 0.97; 95% CI, 0.79-1.18) and 5-year OS (77.9% vs. 78.7%; HR = 0.99; 95% CI, 0.74-1.32).
Patients who received girentuximab achieved a median DFS of 71.4 months (range, 3 months-note reached), whereas the placebo group did not reach a median DFS.
Median OS was not reached in either treatment group.
In total, 569 patients experienced adverse events — including drug-related (21.6%) and serious adverse events (8.4%) — which were evenly divided between arms. The only drug-related serious adverse event observed occurred in one patient assigned placebo.
Researchers evaluated CAIX scores for 849 patients and determined the median CAIX score for the intent-to-treat population was 190 (interquartile range, 120-240). A subgroup analysis of patients with CAIX scores of 200 or greater showed a nonsignificant DFS benefit with girentuximab (HR = 0.75; 95% CI, 0.55-1.04).
“The potential role of CAIX score as a predictor of response to girentuximab would require prospective analysis,” the researchers wrote.
Despite negative trial results, the ARISER study helped to further address the need for an adjuvant therapy in this setting, Martin H. Voss, MD, and Robert J. Motzer, MD, medical oncologists at Memorial Sloan Kettering Cancer Center, wrote in an accompanying editorial.
“We should maximize our understanding of potential biomarkers from previously conducted metastatic trials first, and then optimize design of coming studies in the early-stage perioperative setting,” they wrote. “Ultimately, these many ongoing and future efforts offer hope that we may still extend the success of targeted therapeutics in renal cell carcinoma to a broader patient population.” – by Kristie L. Kahl
Disclosure: Chamie reports research support from UroGen Pharma, grant support from Phase 1 Foundation and Stop Cancer Foundation, consultant roles with Cold Genesys and UroGen Pharma, and a scientific advisory board role with Altor. Please see the full study for a list of all other researchers’ relevant financial disclosures. Voss reports consultant/advisory roles with Calithera, Exelixis, GlaxoSmithKline, Natera and Novartis, as well as research funding directed to Memorial Sloan Kettering Cancer Center from Bristol Meyers Squibb and Genentech/Roche. Motzer reports consultant/advisory roles with Esai, Exelixis, Novartis and Pfizer and research funding directed to Memorial Sloan Kettering Cancer Center from Genentech/Roche, Novartis and Pfizer.
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