NSCLC Studies: Bevacizumab/Pemetrexed Maintenance Improves Survival, KRAS Status Has No Impact on Outcomes with Sorafenib

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Maintenance therapy with bevacizumab (Avastin) plus pemetrexed (Alimta) showed a modest improvement in progression-free survival vs bevacizumab alone in patients with advanced non–small cell lung cancer (NSCLC), according to the final analysis of the AVAPERL study. In a separate study, selecting patients according to KRAS status did not improve outcomes with sorafenib (Nexavar) in advanced NSCLC. Raising more questions than answers, according to expert commentary, both studies were presented as late-breaking abstracts during the 2011 European Multidisciplinary Cancer Congress, held recently in Stockholm and sponsored by the European Society for Medical Oncology, European Cancer Organisation, and the European Society for Radiotherapy and Oncology.

Maintenance Therapy

2.16.1_chart.jpgAVAPERL is a randomized, multicenter, open-label phase III study of 376 patients with advanced, metastatic, or recurrent NSCLC. The study enrolled patients who had achieved disease control (complete or partial remission or stable disease) after one line of bevacizumab/cisplatin/pemetrexed. They were randomly assigned to maintenance therapy with either bevacizumab alone or bevacizumab/pemetrexed and treated until disease progression.

The combination of bevacizumab/pemetrexed as maintenance therapy added 4 months to progression-free survival vs bevacizumab alone, and reduced the risk of progression by 50%. At a median follow-up of 11 months, median progression-free survival was 10.2 months for the combination vs 6.6 months with bevacizumab alone (P < .001), and all subgroups benefitted from the combination vs bevacizumab alone.

Median overall survival had not yet been reached in the combination arm and was 15.7 months in the bevacizumab arm. Median duration of disease control favored the combination arm: 7.8 vs 4.9 months (P < .001). Treatment was well tolerated.

Lead author Fabrice Barlesi, MD, University of Mediterranee-Assistance Publique Hopitaux de Marseille, Marseille, France, said, “Overall, one line of treatment with cisplatin/pemetrexed/bevacizumab followed by continuation maintenance with bevacizumab/pemetrexed is well tolerated and results in the most pronounced reduction in risk of progression in this setting of patients with NSCLC who achieved disease control. Although the number might be viewed as low, 4 months represents a great improvement in the setting of metastatic lung cancer.”

Sorafenib and KRAS Status

In a phase II study of 59 patients with locally advanced NSCLC who experienced disease progression on a previous platinum-containing regimen, and who had KRAS mutation–positive tumors, sorafenib showed some clinical activity. Although the primary endpoint of the study was met (nonprogression rate > 52%), the progression-free survival data are disappointing, with some patients showing rapid progression. However, some heavily treated patients had prolonged benefit from sorafenib.

“Although further study of sorafenib is warranted, we need to identify the subgroups of patients with KRAS mutations who are most likely to benefit. A randomized phase II study should be conduted to investigate whether sorafenib is more active than standard chemotherapy in patients with KRAS-mutated NSCLC,” stated lead author A.M. Dingemans, MD, Maastricht University Hospital, The Netherlands. ■

Disclosure: Dr. Barlesi has disclosed a relationship with Roche and Lilly. Dr. Dingemans received an unrestricted grant from Bayer.

Expert Point of View: NSCLC Studies: Bevacizumab/Pemetrexed Maintenance Improves Survival, KRAS Status Has No Impact on Outcomes with Sorafenib


1. Barlesi F, de Castro J, Dvornichenko V, et al: AVAPERL (MO22089): Final efficacy outcomes for patients with advanced non-squamous non-small cell lung cancer (nsNSCLC) randomised to continuation maintenance (mtc) with bevacizumab (bev) or bev+pemetrexed (pem) after first-line (1L) bev-cisplatin (cis)-pem treatment (Tx). 2011 European Multidisciplinary Cancer Congress. Abstract 34LBA. Presented September 24, 2011.

2. Dingemans AM, Mellema WW, Groen HJM, et al: A phase II study of sorafenib in patients with locally advanced and/or metastatic (stage IIIB or IV) non-small cell lung cancer (NSCLC) with a K-Ras Mutation. 2011 European Multidisciplinary Cancer Congress. Abstract 27LBA. Presented September 24, 2011.