August 2015, Vol 4, No 4
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.
Targeting genetic markers in premalignancy is an emerging concept. In speaking at PMO Live 2015, Scott M. Lippman, MD, said that genetic drivers can identify premalignant conditions and even certain benign conditions, and genetic drivers can aid in identifying higher-risk populations and populations most likely to respond to targeted agents. [ Read More ]
Using less stringent evaluation criteria for sonidegib for the treatment of locally advanced basal cell carcinoma (BCC) improved the complete response (CR) rate observed in the registration trial known as BOLT. These data, presented in poster format, were reported by Michael R. Migden, MD, at the 2015 World Cutaneous Malignancies [ Read More ]