KEY TAKEAWAYS
- NRG Oncology/RTOG1205, was a prospective, phase II, randomized trial aimed to evaluate the safety and efficacy of reirradiation (re-RT) and concurrent bevacizumab (BEV) compared with BEV alone in treating recurrent glioblastoma (GBM).
- Patients were randomly assigned to receive either re-RT, 35 Gy in 10 fractions, with concurrent BEV IV 10 mg/kg once every 2 weeks, or BEV alone until progression.
- The primary objective of the study was to evaluate overall survival (OS), and secondary objectives included progression-free survival (PFS), response rate, and treatment adverse events (AEs), including delayed CNS toxicities.
- The study found that while there was no improvement in OS for BEV + RT compared with BEV alone, the median PFS for BEV + RT was 7.1 months compared with 3.8 months for BEV alone.
- Treatment was well tolerated, with a 5% rate of acute grade 3+ treatment-related AEs and no delayed high-grade AEs.
The purpose of this study was to compare the efficacy of bevacizumab (BEV) with that of BEV alone in treating recurrent glioblastoma (GBM), and to determine whether the combination of the two treatments improved overall survival (OS) and/or progression-free survival (PFS). The primary endpoint was overall survival (OS), and secondary endpoints included progression-free survival (PFS), response rate, and treatment-related adverse events (AEs), such as delayed CNS toxicities.
The NRG Oncology/RTOG1205 study compares re-RT with BEV to BEV alone in a prospective, randomized, phase II trial. Age, degree of resection, and Karnofsky performance status were used as stratification criteria (KPS). Individuals with recurrent GBM were considered if they had imaging evidence of tumor progression less than 6 months after their last round of chemo-RT. Participants were randomly assigned to receive either re-RT (35 Gy in 10 fractions) in conjunction with BEV IV 10 mg/kg once every 2 weeks or BEV alone till progression.
A total of 182 patients were randomly allocated between December 2012 and April 2016, with 170 meetings the inclusion criteria. The features of the patients in each group were comparable. Censored patients had a median follow-up of 12.8 months. Median survival time for BEV + RT was 10.1 months compared to 9.7 months for BEV alone (hazard ratio = 0.98; 80% CI = 0.79 to 1.23; P =.46). With BEV + RT, the median PFS was 7.1 months, compared to 3.8 months with BEV alone (hazard ratio = 0.73; 95% confidence interval = 0.53 to 1.0; P =.05). P =.003 indicates a statistically significant improvement in PFS from 29.1% (95% CI, 19.1 to 39.1) for BEV to 54.3% (95% CI, 43.5 to 65.1%) for BEV + RT over 6 months.
That’s good news: the treatment was well tolerated. There were no serious, long-term side effects from the treatment, and the rate of acute grade 3+ AEs was 5%. A recurrence of GBM was the leading cause of death for most patients. Based on current knowledge, NRG Oncology/RTOG1205 is the first prospective, randomized multi-institutional study to assess the safety and efficacy of re-RT in recurrent GBM employing state-of-the-art RT procedures. Re-RT was shown to be a safe and well-tolerated procedure overall. There was no difference in OS between the two groups. However, the PFS results for BEV + RT were clinically significant, particularly the 6-month PFS rate.
Source: https://pubmed.ncbi.nlm.nih.gov/36260832/
Clinical trial: https://clinicaltrials.gov/ct2/show/NCT01730950
Tsien, C.I., Pugh, S.L., Dicker, A.P., Raizer, J.J., Matuszak, M.M., Lallana, E.C., Huang, J., Algan, O., Deb, N., Portelance, L., Villano, J.L., Hamm, J.T., Oh, K.S., Ali, A.N., Kim, M.M., Lindhorst, S.M. and Mehta, M.P. (2023). NRG Oncology/RTOG1205: A Randomized Phase II Trial of Concurrent Bevacizumab and Reirradiation Versus Bevacizumab Alone as Treatment for Recurrent Glioblastoma. Journal of Clinical Oncology, 41(6), pp.1285–1295. doi:https://doi.org/10.1200/jco.22.00164.
