Depatuxizumab mafodotin does not improve overall survival (OS) when added to radiotherapy and temozolomide in newly diagnosed glioblastoma, according to phase 3 results published in Neuro-Oncology.

Researchers theorized that depatuxizumab mafodotin might benefit patients with glioblastoma because the antibody-drug conjugate targets activated EGFR and EGFR amplification is present in roughly 50% of glioblastomas. 

The researchers tested depatuxizumab mafodotin in a double-blind, phase 3 trial (ClinicalTrials.gov Identifier: NCT02573324) of 639 adults with newly diagnosed glioblastoma and EGFR amplification. 


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The patients’ median age at baseline was 60 (range, 22-84) years, and 62% of patients were men. More than half (53%) of patients had an EGFR variant 3 mutation (EGFRvIII), and 37% had methylated MGMT. 

All patients received radiotherapy plus temozolomide, and they were randomly assigned to receive depatuxizumab mafodotin (n=323) or placebo (n=316). Baseline characteristics were well balanced between the treatment arms. 

At a median follow-up of 18.1 months, OS results were similar between the arms. The median OS was 18.9 months with depatuxizumab mafodotin and 18.7 months with placebo (hazard ratio [HR], 1.02; 95% CI, 0.82-1.26; P =.63). Given the lack of OS benefit, the study was stopped early for futility.

However, progression-free survival (PFS) was longer in patients who received depatuxizumab mafodotin. The median PFS was 8.0 months in the depatuxizumab mafodotin arm and 6.3 months in the placebo arm (HR, 0.84; 95% CI, 0.70-1.01; P =.029). 

PFS was also longer with depatuxizumab mafodotin among patients with an EGFRvIII mutation (HR, 0.72; 95% CI, 0.56-0.93; P =.002) and among those with unmethylated MGMT (HR 0.77, 95% CI 0.61-0.97; P =.012). Depatuxizumab mafodotin did not improve OS for patients with an EGFRvIII mutation or unmethylated MGMT.

The most common adverse events were corneal epitheliopathy and thrombocytopenia. Corneal epitheliopathy occurred in 94% of patients in the depatuxizumab mafodotin arm and 36% of those in the placebo arm. Thrombocytopenia occurred in 61% and 36%, respectively.

Disclosures: This study was supported by AbbVie. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Reference

Lassman AB, Pugh SL, Wang TJC, et al. Depatuxizumab-mafodotin in EGFR-amplified newly diagnosed glioblastoma: A phase III randomized clinical trial. Neuro-Oncology. Published online July 15, 2022. doi:10.1093/neuonc/noac173