Future Horizons in Lung Cancer
Maintenance in NSCLC
Dr Benjamin Besse - Institut Gustave Roussy, Paris, France
I will talk about maintenance within a controversy and my role is to give all the arguments against maintenance. So it doesn’t mean that I’m really against but I have to play the bad guy here. I will give five points against maintenance. The first one is that not everybody will get maintenance, roughly 50% of the patients that start a platinum-based chemotherapy will receive four cycles, will not progress under chemotherapy, will not have a decrease of the performance status and then will be eligible for maintenance. So one point is to understand that maintenance is not for everybody, maintenance is for the ones that receive four cycles of chemotherapy and had benefits from these four cycles. So it’s roughly 50% of the people.
One point also is to say that if you give maintenance it’s because you lose a lot of patients when you give a second line. Without that you lose 30% of the patients but when you look at the numbers in some studies only 9% of patients are lost between first and second line. So if you followed your patients very carefully almost all your patients will receive a second line.
The designs of all the maintenance trials can raise a lot of criticisms. Regarding the switch maintenance, meaning that you receive four cycles of chemotherapy and then you change for a new compound as a maintenance regimen, so this new compound that you did not receive during the four cycles of chemotherapy will be given in the maintenance setting versus in the second line. But, in fact, if you look at the trials usually all the patients in the experimental arm, so in the maintenance arm, will receive the new agent whereas in the control arm patients will receive four cycles of chemotherapy, will wait until progression and only a very small fraction of these patients will eventually receive the active drug that is given in the maintenance setting. So there is really an imbalance – all the patients in the maintenance setting will receive the active drug whereas only 20% of the patients will receive it in the control arm. So this is unfair and my feeling is that the control arm is undertreated so that the trials are eventually positive.
Regarding the maintenance that we call continuation maintenance, pemetrexed is the main drug developed in this setting. If you look at the different trials they also are very impressive: if you give pemetrexed as a maintenance in the PARAMOUNT trial it’s roughly 14 months of overall survival; if you give pemetrexed plus bevacizumab you will reach almost 20 months of overall survival. It’s amazing; it’s very, very strong for a first line chemotherapy regimen. But in fact if you compare these very strong regimens such as bev/carboplatin, bev/carboplatin/pemetrexed, with bev/pemetrexed and maintenance versus the standard one that would be paclitaxel/carboplatin/bevacizumab then the overall survival is exactly the same. The issue is there that in all the maintenance trials usually you randomise after four cycles of chemotherapy so you randomise your base patients, the ones that have really a strong benefit from chemotherapy. In the PointBreak trial where you randomise up front, you select up front, like in the routine if you will give paclitaxel/bevacizumab/carboplatin or pemetrexed/carboplatin/bevacizumab and then in fact the overall survival is exactly the same. So there is really a bias in the way we analyse all these continuation maintenance trials.
My last point is that the field has changed a lot; 20% of the patients will receive targeted therapy up front, probably in the very near future a quarter of the patients will receive an immunotherapy up front so all these trials that were done in the whole population now they have to be rethought in this narrow population that will not be eligible for targeted therapy or an immunotherapy.
