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28-07-2013 | Oncology | Article

Pemetrexed–bevacizumab effective maintenance therapy for NSCLC


Free abstract

medwireNews: Pemetrexed in combination with bevacizumab is superior to bevacizumab alone when given as continuation maintenance therapy in patients with advanced nonsquamous non-small-cell lung cancer (NSCLC), results of the AVAPERL trial show.

Among patients who had achieved disease control with first-line bevacizumab, cisplatin, and pemetrexed as induction therapy, pemetrexed–bevacizumab as maintenance therapy was well tolerated and significantly prolonged progression-free survival (PFS) as compared with bevacizumab alone.

“For most patients with advanced NSCLC who lack [specific] mutations, optimizing treatment options during induction and maintenance remains a priority,” write Fabrice Barlesi (Aix Marseille University, France) and fellow investigators in the Journal of Clinical Oncology. “AVAPERL provides important comparative data from two continuation maintenance regimens.”

This randomized, open-label, multicenter phase III trial included 374 patients with advanced nonsquamous NSCLC from 82 centers in 11 countries. In the induction phase, all patients received four cycles of bevacizumab, cisplatin, and pemetrexed once every 3 weeks; 269 patients (71.9%) achieved disease control, 253 of whom were randomly assigned to receive maintenance therapy with either pemetrexed plus bevacizumab or bevacizumab alone every 3 weeks until disease progression or unacceptable toxicity.

The median time from the end of induction to maintenance was 3 weeks and the median duration of follow up was 8.1 months. The primary endpoint was median PFS, which was significantly longer in patients given pemetrexed–bevacizumab than in those given bevacizumab alone, at 7.4 versus 3.7 months, giving a hazard ratio of 0.48.

Subgroup analyses confirmed that the benefit of combination therapy on PFS was consistent irrespective of patients’ age, performance status, smoking history, and response to induction therapy. Toxicity was greater in the pemetrexed–bevacizumab arm, with a higher frequency of any grade, grade 3/4, and serious adverse events.

Importantly, however, there were no new safety signals. “Longer exposure to maintenance treatment likely accounts for some of the increases in adverse events,” Barlesi and co-authors write. “Examination of the safety analysis suggests that differences in toxicities between arms may largely be the result of toxicities commonly attributed to chemotherapy.”

The team concludes: “Although AVAPERL lacked a pemetrexed-alone arm to allow for direct comparison with this maintenance, comparative data for the two AVAPERL arms support the benefit of maintenance therapy with the combination of bevacizumab and pemetrexed relative to bevacizumab alone in patients with advanced nonsquamous NSCLC.”

medwireNews ( is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2013

By Joanna Lyford, Senior medwireNews Reporter

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