Martin J. van den Bent, MD, professor, Neuro-Oncology, Erasmus MC-Daniel den Hoed Cancer Center, the Netherlands, discusses the combination of temozolomide (Temodal) and depatuxizumab mafodotin (depatux-m) in the treatment of patients with glioblastoma.

Findings from the INTELLANCE 2 trial presented at the 2018 ASCO Annual Meeting showed that the combination of depatux-m and temozolomide resulted in a median 1-year overall survival rate of 40%, compared with 28% in the control arm. This was a randomized phase II trial that tested the antibody-drug conjugate depatux-m alone, depatux-m with temozolomide, and a control arm of either temozolomide or lomustine (Gleostine) alone.

van den Bent says that there a number of questions that have been raised as a result of INTELLANCE 2. The intriguing finding, he says, is the survival benefit with the combination of depatux-m and temozolomide, as this result was seen regardless of the O6-methylguanine-DNA methyltransferase status of the tumor.

An ongoing trial in newly-diagnosed patients with glioblastoma is evaluating the addition of depatux-m to temozolomide and radiation therapy. van den Bent says that this study will show the real power of depatux-m in this tumor type.

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Dr. van den Bent on Temozolomide and Depatux-M in Glioblastoma

Martin J. van den Bent, MD, professor, Neuro-Oncology, Erasmus MC-Daniel den Hoed Cancer Center, the Netherlands, discusses the INTELLANCE 2 trial for recurrent glioblastoma. He presented updated data at the 2018 ASCO Annual Meeting.

About 50% of glioblastoma cases are characterized by 

 mutations, but recent trials with EGFR inhibitors have not worked. Since the introduction of radiotherapy combined with temozolomide (Temodal) as the standard of care, physicians have not made any progress, says van den Bent. INTELLANCE 2, a randomized phase II trial, tests the antibody-drug conjugate depatux-m alone, depatuxizumab mafodotin (depatux-m) with temozolomide, and a control arm of either temozolomide or lomustine (Gleostine) alone.

After a 1-year follow-up, the combination of depatux-m and temozolomide resulted in a median 1-year overall survival rate of 40%, compared with 28% in the control arm. Patients on the combination arm were treated with depatux-m 1 mg/kg every 2 weeks and temozolomide 150 mg-200 mg/kg

Martin J. van den Bent, MD, professor, Neuro-Oncology, Erasmus MC-Daniel den Hoed Cancer Center, the Netherlands, discusses the INTELLANCE 2 trial for recurrent glioblastoma.

Dr. van den Bent on INTELLANCE 2 Trial for Recurrent Glioblastoma

Martin J. Van Den Bent, MD, professor, Neuro-Oncology, Erasmus MC-Daniel den Hoed Cancer Center, the Netherlands, discusses the results of an interim analysis of the randomized phase III CANTON trial, which investigated concurrent and adjuvant treatment with temozolomide (Temodar) in patients with anaplastic glioma without a 1p/19q co-deletion.

A total of 750 patients were enrolled in the trial to address whether concurrent and adjuvant temozolomide would increase survival in this patient population, van den Bent says. Results of a planned interim analysis for efficacy, which was done after 41% of events occurred, showed that adjuvant temozolomide led to an increase in 5-year survival from 44% to 56%. This is associated with a hazard ratio of 0.64 and a 

These findings suggest that adjuvant treatment with temozolomide should become standard of care after radiation therapy for these patients, van den Bent says. However, further follow-up is required to determine what efficacy concurrent use of temozolimide has in this population.

Martin J. Van Den Bent, MD, professor, Neuro-Oncology, Erasmus MC-Daniel den Hoed Cancer Center, the Netherland, discusses the results of an interim analysis of the randomized phase III CANTON trial, which investigated concurrent and adjuvant temozolomide in patients with anaplastic glioma without a 1p/19q co-deletion.

Dr. van den Bent on Adjuvant Temozolomide in Anaplastic Glioma

Martin J. van den Bent, MD, professor, Neuro-Oncology, Erasmus MC-Daniel den Hoed Cancer Center, Rotterdam, The Netherlands, discusses the BELOB trial, which examined bevacizumab versus bevacizumab plus lomustine versus single agent lomustine in patients with recurrent glioblastoma.

Van den Bent says bevacizumab has demonstrated responses in patients with recurrent glioblastoma but it has been unclear so far if it also elicits an increase in overall survival in this population. In trials that examine patients with newly diagnosed glioblastomas, the addition of bevacizumab to radiation and temozolomide increases progression-free survival without effecting overall survival.

The BELOB trial is the first trial that addresses the question of whether bevacizumab helps increase overall survival in recurrent glioblastoma, van den Bent says. This randomized, phase II trial showed that despite the high response rate in bevacizumab treated patients, the overall survival of bevacizumab single-agent patients does not look superior compared to lomustine as a single agent. However, the combination of these two agents demonstrated a benefit, van den Bent says.

At nine months, 38% of patients treated with bevacizumab were alive, 43% of patients treated with lomustine were alive, and 59% of patients treated with the combination of the two agents were alive, van den Bent says.

View more from the 2014 Society for Neuro-Oncology Annual Meeting

Martin J. van den Bent, MD, professor, Neuro-Oncology, Erasmus MC-Daniel den Hoed Cancer Center, Rotterdam, the Netherlands, discusses the BELOB trial, which examined bevacizumab versus bevacizumab plus lomustine versus lomustine single agent in recurrent glioblastoma.

Martin J. van den Bent, MD

Articles

Dr. van den Bent on Temozolomide and Depatux-M in Glioblastoma

Dr. van den Bent on INTELLANCE 2 Trial for Recurrent Glioblastoma

Dr. van den Bent on Adjuvant Temozolomide in Anaplastic Glioma

Dr. van den Bent Discusses Bevacizumab Plus Lomustine in Recurrent Glioblastoma