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Adjuvant Chemo a Winner in Rare Brain Cancer

— Significant survival bump in nondeleted anaplastic glioma

Ƶ MedicalToday

CHICAGO -- Overall and progression-free survival (PFS) improved significantly in patients with a rare form of brain cancer treated with postoperative temozolomide (Temodar), a large, randomized trial showed.

The phase III ended unexpectedly when the first interim data analysis showed a median 5-year survival of 56% for patients who had anaplastic glioma without chromosome 1p/19q co-deletion (nondeleted) treated with radiation therapy followed by temozolomide. That compared with 44% those who did not receive adjuvant temozolomide. The median PFS was 43 months with adjuvant temozolomide and 19 months without.

Action Points

  • Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

Follow-up in the trial will continue to answer a second question addressed by the study: whether concurrent chemoradiation after surgery improves survival in patients with nondeleted anaplastic glioma, as reported here at the American Society of Clinical Oncology annual meeting.

"We know now that temozolomide given after radiation therapy improves survival in this disease," said , of Erasmus MC Cancer Center in Rotterdam, the Netherlands. "Until this study, doctors had no evidence to support the use of adjuvant temozolomide in patients with grade III anaplastic glioma. These findings should expand treatment choices and change the way we treat patients with this rare form of brain cancer."

The results provide an answer to a longstanding question about optimal management of patients with anaplastic glioma, said , of the Mayo Clinic in Rochester, Minn.

"Finally, we have conclusive evidence that the addition of chemotherapy to radiation for patients with anaplastic glioma that are not 1p/19q co-deleted is truly effective," Buckner told Ƶ. "In the past we had evidence for higher-grade gliomas ... so we had often treated patients with anaplastic glioma the same way, but we really didn't know if it was helpful or not.

"This study gives us class I evidence to change treatment clearly to include temozolomide with irradiation for these patients."

Anaplastic astrocytoma, or glioma, is a rare form of brain cancer affecting 1,200 to 1,500 people a year in the U.S. The subtype accounts for a portion of patients who have grade III glioma, which generally has a more favorable prognosis than grade IV glioma.

Previous phase III trials conducted in Europe showed that administration of temozolomide during and after radiation therapy improved outcome in patients with glioblastoma, a relatively chemotherapy-resistant disease. However, administration of chemotherapy after radiotherapy had no impact on outcomes in patients with anaplastic glioma, generally considered to be chemosensitive cancer. The results also showed worse outcomes in patients whose tumors did not have the 1p/19q co-deletion.

"We asked ourselves two questions," van den Bent said. "Would temozolomide given during radiation therapy improve outcome in these patients? Would temozolomide given after radiation therapy improve outcome?

To answer the two questions, researchers designed a four-arm randomized trial involving patients with newly diagnosed World Health Organization grade III glioma without co-deletion. Following curative-intent surgery and adjuvant radiation therapy, patients were randomized to no further treatment, temozolomide administered concurrently with irradiation, 12 months of adjuvant temozolomide, or concurrent temozolomide plus an additional 12 months of adjuvant temozolomide.

Because of the rareness of cancer, investigators required 8 years to accrue 751 randomized patients (December 2007 through September 2015). The trial had a primary endpoint of overall survival (OS).

The first planned interim analysis occurred after a median follow-up of 27 months. Members of the data and safety monitoring committee recommended that the trial be stopped because of the emergence of a significant benefit in favor of adjuvant temozolomide.

"We did not anticipate anything from this interim analysis," van den Bent said. "Usually, these kinds of trials take a long time to produce positive results. We were completely taken by surprise when [the committee] recommended release of the data for adjuvant temozolomide. At no point in time did we anticipate this outcome."

The difference in 5-year survival translated into a 33% reduction in the hazard survival in favor of adjuvant temozolomide as compared with patients who received either surgery alone or surgery plus concurrent chemoradiation (HR 0.67, 95% CI 0.51-0.88, P=0.003). Patients who did not receive adjuvant temozolomide had a median survival of 41 months, whereas the median OS had yet to be reached in patients who received adjuvant chemotherapy.

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    Charles Bankhead is senior editor for oncology and also covers urology, dermatology, and ophthalmology. He joined Ƶ in 2007.

Disclosures

The CATNON study was sponsored by the European Organization for Treatment and Research in Cancer, the Radiation Therapy Oncology Group, Medical Research Council, the Cooperative Trials Group for Neuro-Oncology, and Merck Sharp & Dohme.

Van den Bent disclosed relevant relationships with Merck, Roche, Celldex, Novocure, AbbVie, Amgen, Actelion, and Bristol-Myers Squibb.

Primary Source

American Society of Clinical Oncology

Van den Bent M, et al "Results of the interim analysis of the EORTC randomized phase III CATNON trial on concurrent and adjuvant temozolomide in anaplastic glioma without 1p/19q co-deletion: An Intergroup trial" ASCO 2016; Abstract LBA2000.