Depatuxizumab Mafodotin (Depatux-M) Plus Temozolomide in Recurrent Glioblastoma Patients: Real-World Experience from a Multicenter Study of Italian Association of Neuro-Oncology (AINO)

  • Cancers (Basel). 2021 Jun 3;13(11):2773. doi: 10.3390/cancers13112773.
Marta Padovan  1 ,  Marica Eoli  2 ,  Alessia Pellerino  3 ,  Simona Rizzato  4 ,  Claudia Caserta  5 ,  Matteo Simonelli  6  7 ,  Maria Michiara  8 ,  Mario Caccese  1 ,  Elena Anghileri  2 ,  Giulia Cerretti  1 ,  Roberta Rudà  3  9 ,  Vittorina Zagonel  1 ,  Giuseppe Lombardi  1
Affiliations
  • 1. Department of Oncology, Oncology 1, Veneto Institute of Oncology IOV-IRCCS, 35128 Padua, Italy.
  • 2. Unit of Molecular Neuro-Oncology, Besta-IRCCS, 20133 Milan, Italy.
  • 3. Department of Neuro-Oncology, University and City of Health and Science Hospital, 10126 Turin, Italy.
  • 4. Department of Oncology, Azienda Sanitaria Universitaria Friuli Centrale, 33100 Udine, Italy.
  • 5. Medical Oncology Unit, Azienda Ospedaliera S. Maria, 05100 Terni, Italy.
  • 6. Department of Biomedical Sciences, Humanitas University, 20090 Pieve Emanuele, Italy.
  • 7. IRCCS Humanitas Research Hospital, 20089 Rozzano, Italy.
  • 8. Medical Oncology Unit, University Hospital of Parma, 43126 Parma, Italy.
  • 9. Department of Neurology, San Giacomo Hospital, 31033 Castelfranco Veneto, Italy.
PMID: 34204877 DOI: 10.3390/cancers13112773
Abstract

Background: Depatuxizumab Mafodotin (Depatux-M; ABT-414) is an antibody-drug conjugate consisting of a specific antibody against activated EGFR and a cytotoxic agent with antimicrotubule activity. The INTELLANCE 2/EORTC 1410 phase 2 trial produced interesting results for the combination regimen of Depatux-M and temozolomide in EGFR-amplified glioblastoma patients at first recurrence. For the first time worldwide, our work investigated the clinical outcome and safety of this combination in a real-life population.

Materials and methods: Patients were enrolled from seven AINO (Italian Association of Neuro-Oncology) Institutions. The major inclusion criteria were: histologically confirmed diagnosis of glioblastoma, EGFR-amplified, one or more prior systemic therapies and ECOG PS ≤ 2. According to the original schedule, patients received Depatux-M 1.25 mg/kg every 2 weeks combined with temozolomide. The primary endpoints of the study were overall survival and safety.

Results: A total of 36 patients were enrolled. The median age was 57 years, ECOG PS was 0-1 in 28 patients (88%), MGMT methylated status was found in 22 (64%), 15 patients (42%) received the combined treatment as second-line therapy. The median OS was 8.04 months (95% CI, 5.3-10.7), the 12 month-OS was 37%. On univariate and multivariate analyses, the MGMT methylation status was the only factor resulting significantly associated with survival. Grade 3 ocular toxicity occurred in 11% of patients; no grade 4 ocular toxicity was reported. No death was considered to be drug-related.

Conclusions: The study reported the first "real world" experience of Depatux-M plus temozolomide in recurrent glioblastoma patients. Encouraging clinical benefits were demonstrated, even though most patients were treated beyond second-line therapy. Overall, the results are close to those reported in the previous phase 2 trial. Toxicity was moderate and manageable.

Keywords
Depatux-M; EGFR; antibody drug conjugate; glioblastoma; targeted therapy.
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