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

SIMPLE SUMMARY: Depatux-M is an antibody-drug conjugate against activated EGFR. The efficacy and tolerability of the Depatux-M and temozolomide combination in recurrent glioblastoma patients were recently analyzed in the INTELLANCE-2/EORTC 1410 phase 2 trial. Despite the trial was negative, it showe...

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Autores principales: Padovan, Marta, Eoli, Marica, Pellerino, Alessia, Rizzato, Simona, Caserta, Claudia, Simonelli, Matteo, Michiara, Maria, Caccese, Mario, Anghileri, Elena, Cerretti, Giulia, Rudà, Roberta, Zagonel, Vittorina, Lombardi, Giuseppe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8199759/
https://www.ncbi.nlm.nih.gov/pubmed/34204877
http://dx.doi.org/10.3390/cancers13112773
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author Padovan, Marta
Eoli, Marica
Pellerino, Alessia
Rizzato, Simona
Caserta, Claudia
Simonelli, Matteo
Michiara, Maria
Caccese, Mario
Anghileri, Elena
Cerretti, Giulia
Rudà, Roberta
Zagonel, Vittorina
Lombardi, Giuseppe
author_facet Padovan, Marta
Eoli, Marica
Pellerino, Alessia
Rizzato, Simona
Caserta, Claudia
Simonelli, Matteo
Michiara, Maria
Caccese, Mario
Anghileri, Elena
Cerretti, Giulia
Rudà, Roberta
Zagonel, Vittorina
Lombardi, Giuseppe
author_sort Padovan, Marta
collection PubMed
description SIMPLE SUMMARY: Depatux-M is an antibody-drug conjugate against activated EGFR. The efficacy and tolerability of the Depatux-M and temozolomide combination in recurrent glioblastoma patients were recently analyzed in the INTELLANCE-2/EORTC 1410 phase 2 trial. Despite the trial was negative, it showed interesting results for patients received this combination therapy versus standard treatment. For the first time worldwide, we investigated this treatment in a real-life population. Interestingly, we reported encouraging clinical benefits close to that reported in the previous randomized INTELLANCE 2 trial. Ocular toxicity was manageable. Likely, a subgroup of patients could benefit of this treatment and so, significant molecular predictors of treatment efficacy such as EGFR SNVs should be better investigated in a larger prospective study. 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.
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spelling pubmed-81997592021-06-14 Depatuxizumab Mafodotin (Depatux-M) Plus Temozolomide in Recurrent Glioblastoma Patients: Real-World Experience from a Multicenter Study of Italian Association of Neuro-Oncology (AINO) Padovan, Marta Eoli, Marica Pellerino, Alessia Rizzato, Simona Caserta, Claudia Simonelli, Matteo Michiara, Maria Caccese, Mario Anghileri, Elena Cerretti, Giulia Rudà, Roberta Zagonel, Vittorina Lombardi, Giuseppe Cancers (Basel) Article SIMPLE SUMMARY: Depatux-M is an antibody-drug conjugate against activated EGFR. The efficacy and tolerability of the Depatux-M and temozolomide combination in recurrent glioblastoma patients were recently analyzed in the INTELLANCE-2/EORTC 1410 phase 2 trial. Despite the trial was negative, it showed interesting results for patients received this combination therapy versus standard treatment. For the first time worldwide, we investigated this treatment in a real-life population. Interestingly, we reported encouraging clinical benefits close to that reported in the previous randomized INTELLANCE 2 trial. Ocular toxicity was manageable. Likely, a subgroup of patients could benefit of this treatment and so, significant molecular predictors of treatment efficacy such as EGFR SNVs should be better investigated in a larger prospective study. 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. MDPI 2021-06-03 /pmc/articles/PMC8199759/ /pubmed/34204877 http://dx.doi.org/10.3390/cancers13112773 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Padovan, Marta
Eoli, Marica
Pellerino, Alessia
Rizzato, Simona
Caserta, Claudia
Simonelli, Matteo
Michiara, Maria
Caccese, Mario
Anghileri, Elena
Cerretti, Giulia
Rudà, Roberta
Zagonel, Vittorina
Lombardi, Giuseppe
Depatuxizumab Mafodotin (Depatux-M) Plus Temozolomide in Recurrent Glioblastoma Patients: Real-World Experience from a Multicenter Study of Italian Association of Neuro-Oncology (AINO)
title Depatuxizumab Mafodotin (Depatux-M) Plus Temozolomide in Recurrent Glioblastoma Patients: Real-World Experience from a Multicenter Study of Italian Association of Neuro-Oncology (AINO)
title_full Depatuxizumab Mafodotin (Depatux-M) Plus Temozolomide in Recurrent Glioblastoma Patients: Real-World Experience from a Multicenter Study of Italian Association of Neuro-Oncology (AINO)
title_fullStr Depatuxizumab Mafodotin (Depatux-M) Plus Temozolomide in Recurrent Glioblastoma Patients: Real-World Experience from a Multicenter Study of Italian Association of Neuro-Oncology (AINO)
title_full_unstemmed Depatuxizumab Mafodotin (Depatux-M) Plus Temozolomide in Recurrent Glioblastoma Patients: Real-World Experience from a Multicenter Study of Italian Association of Neuro-Oncology (AINO)
title_short Depatuxizumab Mafodotin (Depatux-M) Plus Temozolomide in Recurrent Glioblastoma Patients: Real-World Experience from a Multicenter Study of Italian Association of Neuro-Oncology (AINO)
title_sort depatuxizumab mafodotin (depatux-m) plus temozolomide in recurrent glioblastoma patients: real-world experience from a multicenter study of italian association of neuro-oncology (aino)
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8199759/
https://www.ncbi.nlm.nih.gov/pubmed/34204877
http://dx.doi.org/10.3390/cancers13112773
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