Abstract
Simple SummaryDepatux-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.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.
Highlights
Glioblastoma (GBM) is the most common and aggressive primary brain tumor
A total of 36 patients were enrolled from seven Institutions of the Italian Association of Neuro-Oncology (AINO) from October 2018 to June 2019
Baseline patient and tumor characteristics are shown in Table 1: the median age was 57 years, the Eastern Cooperative Oncology Group (ECOG) performance status (PS)
Summary
Glioblastoma (GBM) is the most common and aggressive primary brain tumor. While chemoradiotherapy with temozolomide (TMZ) represents standard first-line therapy after surgery [1], the standard of care for second-line treatment has not been defined. Treatment options include re-surgery, re-irradiation and systemic pharmacotherapy—mostly nitrosoureas [2,3]. Bevacizumab demonstrated that it prolongs progression-free survival (PFS) without improving overall survival (OS) [4]; yet, immunotherapy with checkpoint inhibitors showed no efficacy in glioma patients [5,6]. Some recent studies have improved knowledge on molecular pathways and specific gene mutations driving the origin and progression of GBM; we are seeing some promising results due to specific targeted therapies (i.e., BRAF inhibitors, TRK inhibitors and regorafenib) [2,7,8], even though the benefit of these new treatments needs further evaluation. 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.
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