Mark A. Socinski, MD:This patient had a follow-up brain MRI following the SRS treatment. And the rationale for doing that was to make sure that his brain metastases were controlled and that there were no new findings. In this case, there were no new findings, so I would consider this patient safety treated. And the use of bevacizumab, I would say would be safe in this gentleman from a CNS point of view.
The next decision would be on what’s going on in his chest. He had a follow-up CT scan and, not surprisingly, his disease was a little bit worse, both in the primary as well as the mediastinal lymph nodes. He did have a few new nodules in the same lobe as the primary lesion, which is not unusual. And we sometimes see as the brain is getting treated, since the chest hasn’t been treated yet, it’s at risk of progressing. But this patient had pretty minimal disease to start with, so I wouldn’t consider this progression without treatment to be significant.
As I said before, I think his options are either carboplatin with pemetrexed or carboplatin with paclitaxel. The FDA-approved regimen actually with bevacizumab is in combination with carboplatin and paclitaxel. And that patient was treated with that regimen, which I completely agree with. I think it is a category 1 NCCN-recommended regimen. It is based on phase III data. We know that there’s about a 35% response rate from the ECOG 4599 data. It significantly improved PFS, as well as overall survival, in ECOG 4599. So, I’m completely comfortable with his treatment at this time.
In general, what I do is reassess patients typically after 4 cycles. I find that with a regimen like carboplatin/paclitaxel, most patients tolerate 4 cycles relatively well without undue cumulative toxicity. But going beyond 4 cycles, patients start to get into some trouble with cumulative anemia, neuropathy, and fatigue. We had a number of trials done a decade or more ago that looked at either 3 or 4 cycles of platinum-based therapy versus 6 or more. There was no convincing evidence that 6 or more did better from an overall survival point of view or response point of view, maybe a little bit of benefit in PFS. So, I typically stop at 4 cycles. But, again, bevacizumab is a drug that we use until disease progression.
I would continue bevacizumab as a single agent as maintenance therapy. We refer to it as continuation maintenance therapy. And certainly, my experience has been that patients will get several doses. Occasionally, some patients will get a couple years of bevacizumab maintenance benefit. There’s a great deal of variability. And we know from the original ECOG 4599 trial that there were 2- and 3-year survivors remaining on bevacizumab. So, there is a minority of patients who seem to get some long-term benefit from this agent.
Transcript edited for clarity.