Nearly Half Survive 2 Years With GBM Protocol

Major Finding: For newly diagnosed GBM patients, median overall survival reached 21.2 months with a regimen incorporating bevacizumab, temozolomide, irinotecan, and radiation.

Data Source: First 75 patients treated with bevacizumab, temozolomide, and radiation followed by bevacizumab, temozolomide, and irinotecan in a phase II trial.

Disclosures: The investigator-sponsored study received support from Genentech Inc. and Schering-Plough. Dr. Vredenburgh said he consults for Genentech.

CHICAGO — A new protocol that adds temozolomide and radiation to bevacizumab and irinotecan for patients with newly diagnosed glioblastoma multiforme has resulted in median overall survival reaching 21.2 months, according to investigators from Duke University.

At 16 months, 65.3% of the first 75 patients in the up-front, phase II trial were still alive, they reported. The 2-year overall survival rate was 45%.

“We were not surprised by the findings. … We had shown that bevacizumab plus irinotecan had good efficacy in glioblastoma,” said principal investigator Dr. James Vredenburgh, a professor of medicine and the medical director of adult clinical services at Duke University Medical Center.

He suggested that the findings will encourage investigators to enroll patients in phase III studies now underway. “I think the phase III studies will change clinical practice,” Dr. Vredenburgh said.

In May 2009, the Food and Drug Administration approved bevacizumab (Avastin) mono-therapy second-line for treatment of glioblastoma that had progressed after first-line treatment. Temozolomide (Temo-dar) was approved in March 2005 as a first-line treatment with radiation and as a maintenance therapy.

The new experimental protocol uses bevacizumab in combination with temozolomide and radiation therapy, followed by bevacizumab, temozolomide, and irinotecan (Camptosar) for newly diagnosed glioblastoma multiforme and gliosarcoma.

The study rationale was that VEGF (vascular endothelial growth factor) is an essential part of glioblastoma biology, and the anti-VEGF monoclonal antibody bevacizumab has demonstrated synergy with radiation and chemotherapy. Irinotecan was thought possibly to have synergy with temozolomide. Bevacizumab with or without irinotecan had shown activity in recurrent disease, and it was thought that using bevacizumab with chemotherapy in newly diagnosed patients might improve survival.

Using previously reported median survival of 15.8 months in resected patients (N. Engl. J. Med. 2005;352:987-96) as a benchmark, the investigators set the primary end point of this trial as the proportion of patients who were alive 16 months after initiation of combination chemoradiotherapy, with a target of more than 60%.

The study was opened on August 15, 2007, and 75 patients were accrued through September 4, 2008, with a median follow-up of 25 months (range, 19–31 months). A second cohort of 50 patients was enrolled from October 30, 2008, to March 26, 2009. These 50 patients are included in the toxicity data, but not in the survival analysis.

The protocol called for all patients to start receiving radiation therapy and temozolomide at 75 mg/m

After radiation therapy, patients received 6-12 monthly cycles of temozolomide at 200 mg/m

Median progression-free survival reached 14.2 months, and the 2-year progression-free survival rate was 13.3% for the first 75 patients, Dr. Vredenburgh reported.

Median overall survival from progression, which was measured in 62 patients, was 5 months; the 2-year overall survival from progression was 8.8%.

Grade 4 hematologic toxicity occurred in 17 of 125 patients, and deep vein thrombosis/pulmonary embolism occurred in 9 patients.

All other toxicities occurred in not more than two patients. There were four toxic deaths (one each from myocardial infarction, DVT/PE, sepsis, and pneumocystis pneumonia).

Findings should encourage patient enrollment in potentially practice-changing phase III trials.

Source DR. VREDENBURGH

Major Finding: For newly diagnosed GBM patients, median overall survival reached 21.2 months with a regimen incorporating bevacizumab, temozolomide, irinotecan, and radiation.

Data Source: First 75 patients treated with bevacizumab, temozolomide, and radiation followed by bevacizumab, temozolomide, and irinotecan in a phase II trial.

Disclosures: The investigator-sponsored study received support from Genentech Inc. and Schering-Plough. Dr. Vredenburgh said he consults for Genentech.

CHICAGO — A new protocol that adds temozolomide and radiation to bevacizumab and irinotecan for patients with newly diagnosed glioblastoma multiforme has resulted in median overall survival reaching 21.2 months, according to investigators from Duke University.

At 16 months, 65.3% of the first 75 patients in the up-front, phase II trial were still alive, they reported. The 2-year overall survival rate was 45%.

“We were not surprised by the findings. … We had shown that bevacizumab plus irinotecan had good efficacy in glioblastoma,” said principal investigator Dr. James Vredenburgh, a professor of medicine and the medical director of adult clinical services at Duke University Medical Center.

He suggested that the findings will encourage investigators to enroll patients in phase III studies now underway. “I think the phase III studies will change clinical practice,” Dr. Vredenburgh said.

In May 2009, the Food and Drug Administration approved bevacizumab (Avastin) mono-therapy second-line for treatment of glioblastoma that had progressed after first-line treatment. Temozolomide (Temo-dar) was approved in March 2005 as a first-line treatment with radiation and as a maintenance therapy.

The new experimental protocol uses bevacizumab in combination with temozolomide and radiation therapy, followed by bevacizumab, temozolomide, and irinotecan (Camptosar) for newly diagnosed glioblastoma multiforme and gliosarcoma.

The study rationale was that VEGF (vascular endothelial growth factor) is an essential part of glioblastoma biology, and the anti-VEGF monoclonal antibody bevacizumab has demonstrated synergy with radiation and chemotherapy. Irinotecan was thought possibly to have synergy with temozolomide. Bevacizumab with or without irinotecan had shown activity in recurrent disease, and it was thought that using bevacizumab with chemotherapy in newly diagnosed patients might improve survival.

Using previously reported median survival of 15.8 months in resected patients (N. Engl. J. Med. 2005;352:987-96) as a benchmark, the investigators set the primary end point of this trial as the proportion of patients who were alive 16 months after initiation of combination chemoradiotherapy, with a target of more than 60%.

The study was opened on August 15, 2007, and 75 patients were accrued through September 4, 2008, with a median follow-up of 25 months (range, 19–31 months). A second cohort of 50 patients was enrolled from October 30, 2008, to March 26, 2009. These 50 patients are included in the toxicity data, but not in the survival analysis.

The protocol called for all patients to start receiving radiation therapy and temozolomide at 75 mg/m

After radiation therapy, patients received 6-12 monthly cycles of temozolomide at 200 mg/m

Median progression-free survival reached 14.2 months, and the 2-year progression-free survival rate was 13.3% for the first 75 patients, Dr. Vredenburgh reported.

Median overall survival from progression, which was measured in 62 patients, was 5 months; the 2-year overall survival from progression was 8.8%.

Grade 4 hematologic toxicity occurred in 17 of 125 patients, and deep vein thrombosis/pulmonary embolism occurred in 9 patients.

All other toxicities occurred in not more than two patients. There were four toxic deaths (one each from myocardial infarction, DVT/PE, sepsis, and pneumocystis pneumonia).

Findings should encourage patient enrollment in potentially practice-changing phase III trials.

Source DR. VREDENBURGH

Major Finding: For newly diagnosed GBM patients, median overall survival reached 21.2 months with a regimen incorporating bevacizumab, temozolomide, irinotecan, and radiation.

Data Source: First 75 patients treated with bevacizumab, temozolomide, and radiation followed by bevacizumab, temozolomide, and irinotecan in a phase II trial.

Disclosures: The investigator-sponsored study received support from Genentech Inc. and Schering-Plough. Dr. Vredenburgh said he consults for Genentech.

CHICAGO — A new protocol that adds temozolomide and radiation to bevacizumab and irinotecan for patients with newly diagnosed glioblastoma multiforme has resulted in median overall survival reaching 21.2 months, according to investigators from Duke University.

At 16 months, 65.3% of the first 75 patients in the up-front, phase II trial were still alive, they reported. The 2-year overall survival rate was 45%.

“We were not surprised by the findings. … We had shown that bevacizumab plus irinotecan had good efficacy in glioblastoma,” said principal investigator Dr. James Vredenburgh, a professor of medicine and the medical director of adult clinical services at Duke University Medical Center.

He suggested that the findings will encourage investigators to enroll patients in phase III studies now underway. “I think the phase III studies will change clinical practice,” Dr. Vredenburgh said.

In May 2009, the Food and Drug Administration approved bevacizumab (Avastin) mono-therapy second-line for treatment of glioblastoma that had progressed after first-line treatment. Temozolomide (Temo-dar) was approved in March 2005 as a first-line treatment with radiation and as a maintenance therapy.

The new experimental protocol uses bevacizumab in combination with temozolomide and radiation therapy, followed by bevacizumab, temozolomide, and irinotecan (Camptosar) for newly diagnosed glioblastoma multiforme and gliosarcoma.

The study rationale was that VEGF (vascular endothelial growth factor) is an essential part of glioblastoma biology, and the anti-VEGF monoclonal antibody bevacizumab has demonstrated synergy with radiation and chemotherapy. Irinotecan was thought possibly to have synergy with temozolomide. Bevacizumab with or without irinotecan had shown activity in recurrent disease, and it was thought that using bevacizumab with chemotherapy in newly diagnosed patients might improve survival.

Using previously reported median survival of 15.8 months in resected patients (N. Engl. J. Med. 2005;352:987-96) as a benchmark, the investigators set the primary end point of this trial as the proportion of patients who were alive 16 months after initiation of combination chemoradiotherapy, with a target of more than 60%.

The study was opened on August 15, 2007, and 75 patients were accrued through September 4, 2008, with a median follow-up of 25 months (range, 19–31 months). A second cohort of 50 patients was enrolled from October 30, 2008, to March 26, 2009. These 50 patients are included in the toxicity data, but not in the survival analysis.

The protocol called for all patients to start receiving radiation therapy and temozolomide at 75 mg/m

After radiation therapy, patients received 6-12 monthly cycles of temozolomide at 200 mg/m

Median progression-free survival reached 14.2 months, and the 2-year progression-free survival rate was 13.3% for the first 75 patients, Dr. Vredenburgh reported.

Median overall survival from progression, which was measured in 62 patients, was 5 months; the 2-year overall survival from progression was 8.8%.

Grade 4 hematologic toxicity occurred in 17 of 125 patients, and deep vein thrombosis/pulmonary embolism occurred in 9 patients.

All other toxicities occurred in not more than two patients. There were four toxic deaths (one each from myocardial infarction, DVT/PE, sepsis, and pneumocystis pneumonia).

Findings should encourage patient enrollment in potentially practice-changing phase III trials.

Source DR. VREDENBURGH