PointBreak: A Randomized Phase III Study of Pemetrexed Plus Carboplatin and Bevacizumab Followed by Maintenance Pemetrexed and Bevacizumab Versus Paclitaxel Plus Carboplatin and Bevacizumab Followed by Maintenance Bevacizumab in Patients With Stage IIIB or IV Nonsquamous Non-Small-Cell Lung Cancer

PointBreak Is Not Breaking Any Point in NSCLC!

The randomized phase III PointBreak trial recently published in JCO compared the old standard carboplatin–paclitaxel–bevacizumab followed by bevacizumab maintenance with carboplatin–pemetrexed–bevacizumab followed by pemetrexed–bevacizumab maintenance in first-line, stage III/IV non-squamous NSCLC. The primary endpoint of superior OS (intent-to-treat population) in the pemetrexed-based regimen was not met, with a hazard ratio of 1. Response rate showed no difference between the two regimens. The only difference was in PFS in favor of the pemetrexed–bevacizumab arm, with a modest but significant 17% reduction in the risk of progression. The PFS benefit was not surprising considering the data from PARAMOUNT (pemetrexed maintenance vs placebo) and AVAPERL (pemetrexed–bevacizumab maintenance vs bevacizumab maintenance) and what has been reported in colorectal cancer. This PFS benefit of PointBreak translated into a possible OS benefit for the patients who entered the maintenance part in an exploratory analysis and would be in line with the AVAPERL trial. No new safety signal has been reported between the two regimens tested. A cost analysis would be of interest, considering the higher cost of pemetrexed vs paclitaxel in the present economic context, where increased cost can only be justified by added medical value.

Overall, the now 8-year-old carboplatin–paclitaxel–bevacizumab followed by bevacizumab maintenance remains an option and has not been clearly beaten by other regimens or strategies.