From the Guidelines
The recommended second-line treatment for Glioblastoma Multiforme (GBM) after failed first-line therapy is bevacizumab (Avastin) or lomustine (CCNU), with the choice of treatment depending on the patient's performance status, time since initial treatment, pattern of recurrence, and molecular characteristics of the tumor. According to the most recent and highest quality study 1, bevacizumab is commonly used as a second-line option, typically administered at 10 mg/kg intravenously every 2 weeks until disease progression or unacceptable toxicity. Lomustine is another option, given orally at 100-130 mg/m² every 6 weeks. Some oncologists use combination approaches such as bevacizumab with lomustine or temozolomide rechallenge with a dose-dense regimen (75-100 mg/m² for 21 days of a 28-day cycle).
Key Considerations
- Treatment selection depends on the patient's performance status, time since initial treatment, pattern of recurrence, and molecular characteristics of the tumor 1.
- Tumor treating fields (TTFields/Optune) may be continued if used in first-line therapy.
- Clinical trial enrollment should be strongly considered when available, as standard second-line options offer limited survival benefit 1.
- The poor response to second-line therapy reflects GBM's aggressive nature and ability to develop treatment resistance through multiple molecular pathways, explaining why no single approach has demonstrated clear superiority in extending overall survival.
Alternative Options
- Repeat surgery and implantation of carmustine-impregnated polymers may lead to marginal prolongation of survival compared with placebo, as demonstrated in a randomised trial conducted in the early 1990s 1.
- Re-irradiation is being considered increasingly for recurrent small tumours, although there is considerable doubt about its benefit and the literature lacks prospective and comparative trials 1.
Evidence-Based Recommendations
The recommendations are based on the most recent and highest quality study 1, which provides guidance on the diagnosis, treatment, and follow-up of high-grade glioma, including GBM. The study highlights the limited survival benefit of standard second-line options and the importance of considering clinical trial enrollment.
From the FDA Drug Label
2.4 Recurrent Glioblastoma The recommended dosage is 10 mg/kg intravenously every 2 weeks. 14.1 Newly Diagnosed Glioblastoma Multiforme ... At the time of disease progression, temozolomide was administered as salvage therapy in 161 patients of the 282 (57%) in the RT alone arm, and 62 patients of the 277 (22%) in the temozolomide+RT arm
The recommended second-line treatment for Glioblastoma Multiforme (GBM) after failed first-line therapy is bevacizumab at a dose of 10 mg/kg intravenously every 2 weeks 2 or temozolomide as salvage therapy 3.
- Bevacizumab is indicated for the treatment of recurrent glioblastoma (GBM) in adults.
- Temozolomide can be used as salvage therapy at the time of disease progression.
From the Research
Recommended Second-Line Treatment for Glioblastoma Multiforme (GBM)
The recommended second-line treatment for GBM after failed first-line therapy is a topic of ongoing research and debate. Based on the available evidence, the following points can be made:
- Bevacizumab (BEV) is widely used for the treatment of patients with recurrent GBM 4, 5, 6, 7.
- Lomustine (CCNU) monotherapy is an approved chemotherapeutical option for recurrent GBM 4, 5, 6, 8.
- The combination of BEV and CCNU has been shown to be effective in treating recurrent GBM, with improved progression-free survival (PFS) and overall survival (OS) compared to BEV monotherapy 4, 5.
- A meta-analysis of six clinical trials found that the combination of lomustine and BEV improved OS, PFS, and 6-month PFS in patients with GBM 5.
- Another study found that the combination of lomustine and BEV was well-tolerated, although hematological toxicity may be a dose-limiting factor 6.
- A 2-cohort study found that bevacizumab/irinotecan (BI) had higher response rates and longer OS compared to procarbazine/lomustine/vincristine (PCV) in patients with recurrent GBM 7.
- Lomustine has become a standard of care in recurrent GBM, with activity largely restricted to patients with tumors with O6-methylguanine DNA methyltransferase (MGMT) promoter methylation 8.
Key Findings
- The combination of BEV and CCNU is a recommended second-line treatment for GBM after failed first-line therapy.
- Lomustine monotherapy is also an option for recurrent GBM.
- The choice of treatment should be based on individual patient characteristics, including tumor biology and prior treatment history.
- Further research is needed to determine the optimal treatment strategy for GBM and to improve patient outcomes.
Treatment Options
- Bevacizumab (BEV) plus lomustine (CCNU)
- Lomustine (CCNU) monotherapy
- Bevacizumab/irinotecan (BI)
- Procarbazine/lomustine/vincristine (PCV)