NSCLC with Multiple Sites of Metastasis and No Driver Mutation - Episode 4
Mark A. Socinski, MD:As previously stated, bevacizumab has 4 positive phase III trials showing that it improves outcomes whether you look at response, progression-free survival, or, in 2 of the trials, overall survival. So, I definitely think it’s an option for patients who are eligible to receive it.
You have to be selective in patients who you recommend this drug in. There are lots of reasons not to use it. But in patients who don’t have the reasons not to use it, I think it’s an important part of their treatment regimen. The typical toxicities are risk of bleeding, particularly hemoptyses; the boxed warning includes GI perforation, that’s an uncommon event. I’ve certainly seen that in my practice, but it’s quite uncommon. There are no ways to predict that. Hypertension is an issue that you have to be aware of and follow, although it’s usually not unmanageable. You have to be careful in following renal function on patients and looking for proteinuria.
There are a number of very uncommon things, like reversible posterior leukoencephalopathy and other things, that happen with this drug, but they’re exceedingly uncommon. And for the most part bevacizumab is a relatively well-tolerated agent as a single agent. Our strategy with bevacizumab when we use it with carboplatin/paclitaxel is I typically administer 4 cycles. And then, I would continue bevacizumab as maintenance therapy until disease progression. I find that once patients get to that maintenance part of treatment, and they’re only receiving the bevacizumab and not the carboplatin/paclitaxel, they tolerate it exceedingly well. So, I think, in general, it’s a well-tolerated agent.
The initial trial ECOG 4599, which tested the addition of bevacizumab to carboplatin/paclitaxel, excluded patients with brain metastases because there were some early issues regarding the safety in that population. So, when bevacizumab was approved in nonsquamous nonsmall-cell lung cancer around 2005, it was initially approved in patients who did not have presence of brain metastases. If you look at the nonsquamous population, about 20% of them have brain metastases at the time of diagnosis.
We actually early on launched a trial called the PASSPORT trial. And the primary objective of the PASSPORT trial was to see if you could safely give bevacizumab in patients in the first- or second-line setting of treated brain metastases. We treated, I think, 116 patients where the primary endpoint of the trial was rate of CNS hemorrhage, and we saw no significant CNS hemorrhage. And so, actually the label was changed based on the PASSPORT trial and, as I stated earlier, that we have established safety. If the brain metastases are treated and controlledand we know that this gentleman had a follow-up MRI that showed no new brain lesions following his stereotactic radiosurgery—under those conditions, I would say that bevacizumab is safe in this setting. Initially, this was an agent that we very cautiously used in patients with a brain metastases. We don’t have any studies about the safety of bevacizumab in patients who have untreated brain metastasis. And that’s why earlier in the case discussion I said that treating the brain metastases, if you’re considering using bevacizumab, is a critical part of management.
Transcript edited for clarity.