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 toKRASstatus 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
AVAPERL 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
References
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.
