August 2015, Vol 4, No 4

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IDH1 Gene and ATRX Gene Prognostic in Anaplastic Astrocytoma


The IDH1 gene and the ATRX gene appear to be potential prognostic markers for anaplastic astrocytoma, a rare form of brain cancer, according to findings of a phase 3 trial. Patients with a mutated IDH1 gene survived for a mean of 7.9 years after diagnosis versus 2.8 years for patients with an unaltered IDH1 gene (P = .006). Those with a mutated ATRX gene survived a mean of 9.4 years versus 3.9 years for an unaltered ATRX gene (P = .008).

Analysis of IDH1 and ATRX status and correlation with survival was done as part of the RTOG9813 trial, which included 201 patients with newly diagnosed anaplastic astrocytoma between 2002 and 2007. Accrual was poor in this trial, said lead author Susan Marina Chang, MD, Director of the Neuro-Oncology Division at the University of California at San Francisco.

The analysis of ATRX status and end points is still ongoing.

Patients were randomized to radiation plus temozolomide versus radiation plus nitrosourea. Standard radiation was delivered at 59.4 Gy (1.8 Gy in 33 fractions) 5 days a week for 6 weeks.

“If these findings are verified, they could influence on patient care,” said study coauthor Arnab Chakravarti, MD, Director of the Brain Tumor Program at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute.

About 50% of patients in both arms had a mutated IDH1 gene. Mean age was about 43 years, and more than 95% had dominant anaplastic astrocytoma histology.

At a median follow-up of 3.6 years, 128 deaths had occurred. As of October 2014, 68 patients were alive (median follow-up of 9.1 years). There was no difference in overall survival between the 2 treatment arms: 3.9 years with temozolomide and 3.8 years with nitrosourea. No difference in progression-free survival was observed between treatment arms. A trend was found toward improved survival in patients with a mutated IDH1 gene treated with radiation plus temozolomide versus radiation plus nitrosourea.

ATRX mutation status also was predictive for survival in this study: median overall survival was 9.4 years versus 3.9 years (P = .008). The analysis of this mutation and its correlation with other end points is ongoing.

Nitrosourea therapy was associated with greater toxicity and compromised ability to complete chemotherapy. Completion rates, >95%, were excellent for radiation therapy; 60% of patients in the temozolomide arm completed chemotherapy compared with 21.4% in the nitrosourea arm. Grade 3/4 hematologic toxicity was greater with nitrosourea: 47.9% for temozolomide versus 75.8% for nitrosourea.

This is the only randomized prospective trial to compare these 2 chemotherapies in this disease. This study highlights the importance of molecular analysis. In this study, a limitation is that prospective tissue collection was not mandated, limiting correlative analysis, Dr Chang said.

Interview with the Innovators - August 24, 2015

Challenges in Treating Multiple Myeloma and the Impact of New Oral Oncolytics

An Interview with Dixie-Lee Esseltine, MD, and George Mulligan, PhD, of Takeda Pharmaceuticals Multiple myeloma (MM) is a difficult cancer to treat as it is heterogeneous in nature. Each line of therapy pre­sents many choices for physicians and their patients, making it challenging to know which treatment is best for [ Read More ]

Uncategorized - August 24, 2015

Molecular Subtype-Specific Therapy in DLBCL

Molecular classification of diffuse large B-cell lymphoma (DLBCL), the most common type of non-Hodgkin lymphoma, is beginning to influence treatment selection and hopefully will improve outcomes, according to presenters at an education session. Cell-of-origin (COO) identification by genetic analysis has enabled classification of DLBCL into 2 subtypes that have different [ Read More ]