Hint of survival benefit with bevacizumabpemetrexed maintenance for NSCLC

Updated data from the phase III AVAPERL trial hint that there might be an overall survival (OS) benefit of using bevacizumab in combination with pemetrexed as maintenance therapy in patients with advanced nonsmall cell lung cancer (NSCLC).

“The AVAPERL study was not powered to detect differences in OS between treatment arms”, Fabrice Barlesi, of Aix Marseille University in France, and colleagues observe in the Annals of Oncology.

“The analysis revealed, however, that OS was numerically increased by nearly 4 months in patients treated with maintenance bevacizumab-pemetrexed as compared with bevacizumab alone”, the international team of researchers reports.

OS was longer if the combination therapy was given rather than single-agent bevacizumab from both the start of induction therapy (19.8 vs 15.9 months) and the time of randomisation to maintenance treatment (17.1 vs 13.2 months). This is noteworthy, the team suggests, because the median duration of OS seen in trials using pemetrexed as single agent maintenance therapy has ranged from around 13.9 to 15.5 months.

One-year and 2-year OS were 67.7% and 34.1%, respectively, for the combination maintenance treatment and 71.5% and 39.7% for single-agent bevacizumab.

The aim of the AVAPERL trial was to determine if the combined use of bevacizumab and pemetrexed would have any further benefits over using bevacizumab alone as maintenance treatment for advanced NSCLC. Patients were eligible for inclusion if they had previously untreated, inoperable, locally advanced or recurrent metastatic disease.

A total of 376 patients were enrolled and given induction therapy consisting of four cycles of bevacizumab 7.5 mg/kg, cisplatin 75 mg/kg, and pemetrexed 500 mg/m2 given intravenously on day 1 every 3 weeks. Patients with an objective response were then randomised to either continue bevacizumab alone or in combination with pemetrexed.

The primary endpoint of the trial was progression-free survival (PFS). This was significantly improved by the combined use of bevacizumab and pemetrexed versus bevacizumab alone (7.4 vs. 3.7 months).

No new safety concerns emerged in the updated analysis, the researchers note.

They conclude: “In an unselected population of [nonsquamous] NSCLC patients achieving disease control on platinum-based induction therapy, maintenance with bevacizumab-pemetrexed was associated with a non-significant increase in OS over bevacizumab alone.”

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