Second-line bevacizumab plus irinotecan extends survival of patients with glioblastoma

The combination of bevacizumab and irinotecan (BEV+IRI) as second-line treatment of glioblastoma (GBM) results in better median progression-free (PFS) and overall survival (OS) when compared with historical controls, and its toxicity profile is comparable to published data, reports a study.

“However, BEV+IRI is a regimen with activity in recurrent GBM and its toxicity is considered acceptable given the extremely unfavourable prognosis associated with this tumour,” said the researchers led by R. Ranchor from Centro Hospitalar Universitário do Porto, Porto, Portugal.

The study was presented by co-author MJ Magalhaes, also from Centro Hospitalar Universitário do Porto, at the recent ESMO Sarcoma and Rare Cancers Congress 2023 in Lugano, Switzerland.

As evidence for second-line treatment remains contentious and no standard of care is established, Ranchor, Magalhaes, and their colleagues had conducted this retrospective analysis to provide real-world evidence on the use of BEV+IRI as second-line treatment of GBM.

Adult patients with a first recurrence of a GBM, following treatment with Stupp protocol, were identified for this study. The researchers then selected those treated with second-line BEV+IRI therapy (10 mg/kg and 125 mg/m², respectively, every 2 weeks) between 2011 and 2020 at their institution.

Medical records were used to obtain patient data. In addition, the Kaplan-Meier method was used to assess both PFS and OS.

Forty-two patients were eligible for inclusion, of whom 26 (62 percent) were men, with a median age of 53 years. Nearly half of the patients (n=17, 40 percent) had frontal localization of GBM. [ESMO Sarcoma 2023, abstract 3P]

All patients received second-line BEV+IRI, with a mean of 19 cycles, but four of them required a 20-percent dose reduction of IRI due to severe thrombocytopenia in two and deterioration of ECOG performance status in another two.

The objective response rate was 37 percent at 3 months and 7 percent at 6 months based on response evaluation by magnetic resonance imaging. No cases of complete response with the combination therapy were observed.

The median PFS was 7 months (95 percent confidence interval [CI], 2.966‒11.034), with a 6-month PFS of 81 percent, and the median OS was 8.5 months (95 percent CI, 6.766‒15.234), with a 6-month OS of 59.5 percent, 1-year OS of 43 percent, and 2-year OS of 21 percent.

In terms of safety, fatigue (n=35, 83 percent) was the most common toxicity, followed by diarrhoea (n=26, 62 percent), anaemia (n=23, 55 percent), and thrombocytopenia (n=19, 45 percent).

“In this analysis, [median] PFS and OS were longer than the historical control group (PFS: 7 vs 4 months [RTOG 0625]; OS: 8.5 vs 7.7 months [RTOG 0625]),” the researchers said. “Toxicity profile was consistent with previously published data, but not insignificant.”

The most common primary malignant brain tumour in adults, GBM is characterized by an aggressive behaviour and is associated with a poor prognosis. Nearly all patients (90 percent) develop recurrence or progression after the first-line standard treatment with Stupp protocol, according to the researchers.