Phase 2 Study of a Temozolomide-Based Chemoradiation Therapy Regimen for High-Risk, Low-Grade Gliomas: Long-Term Results of Radiation Therapy Oncology Group 0424

• Published in: International journal of radiation oncology, biology, physics Vol. 107; no. 4; pp. 720 - 725
• Main Authors: Fisher, Barbara J., Pugh, Stephanie L., Macdonald, David R., Chakravatri, Arnab, Lesser, Glenn J., Fox, Sherry, Rogers, C. Leland, Werner-Wasik, Maria, Doyle, Thomas, Bahary, Jean-Paul, Fiveash, John B., Bovi, Joseph A., Howard, Steven P., Michael Yu, Hsiang-Hsuan, D’Souza, David, Laack, Nadia N., Barani, Igor J., Kwok, Young, Wahl, Daniel R., Strasser, Jon F., Won, Minhee, Mehta, Minesh P.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.07.2020
• Subjects: Adult; Brain Neoplasms - pathology; Brain Neoplasms - therapy; Chemoradiotherapy; Female; Glioma - pathology; Glioma - therapy; Humans; Kaplan-Meier Estimate; Male; Neoplasm Grading; Progression-Free Survival; Temozolomide - therapeutic use
• ISSN: 0360-3016; 1879-355X
• DOI: 10.1016/j.ijrobp.2020.03.027

To report the long-term outcomes of the RTOG 0424 study of a high-risk, low-grade glioma population treated with concurrent and adjuvant temozolomide (TMZ) and radiation therapy (RT). For this single-arm, phase 2 study, patients with low-grade gliomas with ≥3 risk factors (age ≥40 years, astrocytoma, bihemispheric tumor, size ≥6 cm, or preoperative neurologic function status >1) received RT (54 Gy in 30 fractions) with TMZ and up to 12 cycles of post-RT TMZ. The initial primary endpoint P was overall survival (OS) at 3 years after registration. Secondary endpoints included progression-free survival (PFS) and the association of survival outcomes with methylation status. The initial 3-year report of this study was published in 2015. The study accrued 136 patients, of whom 129 were analyzable. The median follow-up for surviving patients was 9.0 years. The 3-year OS was 73.5% (95% confidence interval, 65.8%-81.1%), numerically superior to the 3-year OS historical control of 54% (P < .001). The median survival time was 8.2 years (95% confidence interval, 5.6-9.1). Five- and 10-year OS rates were 60.9% and 34.6%, respectively, and 5- and 10-year PFS rates were 46.8% and 25.5%, respectively. The long-term results confirmed the findings from the initial report for efficacy, suggesting OS and PFS outcomes with the RT-TMZ regimen exceeded historical control groups treated with radiation alone. Toxicity was acceptable.